Patient Name Report DateTumor TypeBone marrowmultiple myeloma

Electronically Signed by Jeffrey S. Ross M.D., Medical Director | CLIA Number: 22D2027531 | Foundation Medicine, Inc., 150 2nd Street, 1st Floor, Cambridge, MA 02141 | 1.888.988.3639 page 1 of 14

Date of Birth Medical Facility Specimen Received

Sex Ordering Physician Specimen Site Bone MarrowFMI Case #

Female

Additional Recipient Date of Collection

Medical Record # Medical Facility ID # Specimen Type Aspirate

Specimen ID Pathologist

ABOUT THE TEST:FoundationOne Heme is a next-generation sequencing (NGS) based assay that identifies genomic alterations within hundreds of cancer-related genes.

All Report Updates

Amended Report 6/30/2014

Note: This is a QUALIFIED report. This specimen failed to meet minimum performance standard following sequencing. We can confirm the presence of the genomic alterations detailed in this report, but the data obtained were insufficientfor comprehensive detection of genomic alterations.

PATIENT RESULTS TUMOR TYPE: BONE MARROW MULTIPLEMYELOMA

3 genomic alterations Genomic Alterations Identified†

IGH IGH-MMSET (WHSC1) and IGH-FGFR3rearrangementTP53 C277*, S166*

2 therapies associated with potential clinical benefit

0 therapies associated with lack of response

2 clinical trials

†For a complete list of the genes assayed, please refer to the Appendix⌘See Appendix for details

THERAPEUTIC IMPLICATIONS

Genomic Alterations Detected

FDA Approved Therapies(in patient’s tumor type)

FDA Approved Therapies(in another tumor type)

Potential Clinical Trials

IGHIGH-MMSET (WHSC1) andIGH-FGFR3 rearrangement

None PazopanibPonatinib

Yes, see clinical trialssection

TP53C277*, S166*

None None None

Patient Name Report DateTumor TypeBone marrowmultiple myeloma

Electronically Signed by Jeffrey S. Ross M.D., Medical Director | CLIA Number: 22D2027531 | Foundation Medicine, Inc., 150 2nd Street, 1st Floor, Cambridge, MA 02141 | 1.888.988.3639 page 2 of 14

Note: Genomic alterations detected may be associated with activity of certain FDA approved drugs; however, the agents listed in this report may havevaried clinical evidence in the patient’s tumor type. Neither the therapeutic agents nor the trials identified are ranked in order of potential or predictedefficacy for this patient, nor are they ranked in order of level of evidence for this patient’s tumor type.

Patient Name Report DateTumor TypeBone marrowmultiple myeloma

Electronically Signed by Jeffrey S. Ross M.D., Medical Director | CLIA Number: 22D2027531 | Foundation Medicine, Inc., 150 2nd Street, 1st Floor, Cambridge, MA 02141 | 1.888.988.3639 page 3 of 14

GENOMIC ALTERATIONS

GENEALTERATION

INTERPRETATION

IGHIGH-MMSET(WHSC1) and IGH-FGFR3rearrangement

IGH (immunoglobulin heavy chain) gene codes for the heavy chain component of antibodies1. Duringantibody diversification, the IGH locus undergoes recombination and somatic hypermutation, remodelingevents that are susceptible to aberrant rearrangement with other parts of the genome2,3,4. Because theIGH locus contains multiple strong transcriptional enhancers, IGH-involving rearrangements frequentlyresult in aberrant up-regulation of gene expression within rearranged regions. IGH-involvingrearrangements are frequent in multiple myeloma (MM) patients, with an incidence of 55–65% inintramedullary myeloma, 70–80% in extramedullary myeloma, and >90% in myeloma cell lines5,6,7,8. InMM, the most frequent IGH-involving rearrangements are with 11q13 (MYEOV and CCND1), 4p16(FGFR3 and MMSET), 16q23 (MAF), 6p21 (CCND3) and 20q12 (MAFB)9. The rearrangement in thistumor is between the IGH locus (14q32) and 4p16; it is similar to t(4;14) which is reported in 15-21% ofMM cases and is an indicator of poor prognosis, especially when treatment regimens do not includelenalidomide and bortezomib9,10,11. Virtually all MM samples and cell lines with t(4;14) have been reportedto overexpress MMSET (also known as WHSC1 and NSD2) from an IGH enhancer12,13. The MMSETgene leads to a production of multiple protein isoforms, some of which have histone methyltransferase(HMT) activity and several that have the capability to function as transcriptional repressors14,15,16,17,18.Although the precise mechanisms of MMSET pathogenesis are not clear, forced down-regulation ofMMSET has been reported to block proliferation of MM cell lines and MM xenografts16,19,20. MMSEToverexpression has also been reported in a range of solid tumors, frequently associated with tumoraggressiveness and/or poor prognosis21,22,23,24,25. In addition to MMSET, 75-80% of samples with t(4;14)also overexpress FGFR312,26,27. FGFR3 encodes a member of the fibroblast growth factor receptor family,which are cell surface tyrosine kinase receptors. The FGFR family plays an important role in celldifferentiation, growth and angiogenesis through binding of 20 various FGF ligands and the subsequentactivation of signaling pathways28. FGFR3 overexpression does not have strong prognostic significancewithin the t(4;14) MM10,14,29,30. However, overexpression of FGFR3 in some cultured cell systems andmice leads to transformation and leukemia/lymphoma development31,31,32,33, whereas inhibition of FGFR3is effective against t(4;14) MM cell lines and xenograft models overexpressing FGFR312,27,34. Thissuggests that FGFR3 contributes to the pathogenesis of t(4;14) MM in at least a subset of cases andinhibition of FGFR3 may benefit patients with a t(4;14) rearrangement. There are currently no approvedtherapies that directly target IGH rearrangements or MMSET overexpression. However, tumors withFGFR3 activation or overexpression may be sensitive to FGFR family inhibitors, including pazopanib andponatinib. In addition, BET domain inhibitors have been reported to block IGH-mediated transcriptionalactivation for an IGH-MYC rearrangement in an MM cell line35 and may be effective in negating IGH-driven transcriptional deregulation here. However, because it is not known whether this tumor exhibitsoverexpression of FGFR3, or whether the FGFR3 mutation in this tumor activates FGFR3 signaling, it isnot known whether this approach would be beneficial here.

TP53C277*, S166*

Loss of the tumor suppressor p53, which is encoded by the TP53 gene, is common in aggressiveadvanced cancers36. TP53 truncation mutations before or within the DNA-binding domain (DBD, aa 100-300) of the p53 protein would disrupt the DBD and the tetramerization domain37. These types ofmutations, such as observed here, are thought to dysregulate the transactivation of p53-dependent genesand are predicted to promote tumorigenesis38,39. TP53 point mutations and deletions are rare in the earlystages of multiple myeloma (MM), occurring in 3-5% and 11%, respectively of newly diagnosed cases40,41,42. However, as the disease progresses and/or relapses, inactivating alterations of p53, includingdeletions and point mutations are reported more frequently (15-46%) and have been associated with poorprognosis41,43,44,45,46(reviewed in Sawyer 2011; 21356186). For example, one study examining theassociation of TP53 with response to lenalidomide in relapsed/refractory MM reported shorter progressionfree survival (PFS; 3.4 vs. 11-11.1 months) and overall survival (OS) (7.2-12.1 vs. 28.8 months) inpatients with a TP53 alteration44. Other studies also reported shorter OS (22-26.6 vs. 41-48.5 months) forMM patients with TP53 alterations41,45. TP53 alterations are even more frequent following thetransformation of MM to plasma cell leukemia (PCL), with a single allele alteration being reported in 46-83% and bi-allelic inactivation in 33% of the PCL cases, although unlike for MM, neither bi- or mono-allelic loss of TP53 exhibits prognostic value in PCL43,47,48. Germline mutations in TP53 are associatedwith the very rare disorder Li-Fraumeni syndrome and the early onset of many cancers49,50. Estimates for

Patient Name Report DateTumor TypeBone marrowmultiple myeloma

Electronically Signed by Jeffrey S. Ross M.D., Medical Director | CLIA Number: 22D2027531 | Foundation Medicine, Inc., 150 2nd Street, 1st Floor, Cambridge, MA 02141 | 1.888.988.3639 page 4 of 14

the prevalence of germline TP53 mutations in the general population range from 1:5,00051 to 1:20,00052,and in the appropriate clinical context germline testing of TP53 is recommended. At present, there are noapproved treatments or clinical trials focused on targeting TP53 alterations in myeloma. However, severaltherapeutic approaches are under examination for MM patients with TP53 mutation53.

Patient Name Report DateTumor TypeBone marrowmultiple myeloma

Electronically Signed by Jeffrey S. Ross M.D., Medical Director | CLIA Number: 22D2027531 | Foundation Medicine, Inc., 150 2nd Street, 1st Floor, Cambridge, MA 02141 | 1.888.988.3639 page 5 of 14

THERAPIES

There are no therapies FDA approved in this patient's tumor type that are specific to the reported genomic alterations.

ADDITIONAL THERAPIES – FDA APPROVED IN OTHER TUMOR TYPES THERAPY RATIONALE

Pazopanib

Pazopanib is a tyrosine kinase inhibitor that targets VEGFR1/2/3, PDGFR-alpha, FGFR1/3, Kit, Itk, Lck,and c-Fms. Pazopanib is FDA approved for the treatment of advanced renal cell carcinoma and softtissue sarcomas that have progressed after prior chemotherapy. Amplification, overexpression, orconstitutive activation of FGFR3 may predict sensitivity to pazopanib. Multiple FGFR3 inhibitors havebeen reported effective at inhibiting proliferation of multiple myeloma cell lines with FGFR3overexpression and/or activating mutation12. Pazopanib is currently in clinical trials in multiple cancertypes. Pazopanib was reported to exhibit activity against multiple myeloma cells in vitro but a phase 2study of pazopanib in patients with relapsed or refractory multiple myeloma reported no clinical responses54. However, because it is not known whether this tumor exhibits overexpression of FGFR3, it is unclearthat this approach would be beneficial here.

Ponatinib

Ponatinib is a multi-kinase inhibitor targeting BCR-ABL, RET, KIT, FLT-3, PDGFRs, VEGFRs, FGFRs,and other tyrosine kinases. Ponatinib was approved by the FDA for use in advanced, T315I-mutatedchronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia(Ph+ ALL), as well as for CML and Ph+ ALL patients for whom no other tyrosine kinase inhibitor isindicated. Amplification, overexpression, or constitutive activation of FGFR3 may predict sensitivity toponatinib (Schrock et al., AACR Abstract 2083)55. Multiple FGFR3 inhibitors have been reported effectiveat inhibiting proliferation of multiple myeloma cell lines with FGFR3 overexpression and/or activatingmutation12. Ponatinib has shown efficacy in blocking FGF2/FGFR3-mediated survival of CML cells invitro, as well as elicited responses in FGF2-expressing CML patients, including those with FGFR3activating mutations56. However, because it is not known whether this tumor exhibits overexpression ofFGFR3, it is not clear that this approach would be beneficial here.

Genomic alterations detected may be associated with activity of certain FDA approved drugs, however the agents listed in this report may have little orno evidence in the patient’s tumor type

Patient Name Report DateTumor TypeBone marrowmultiple myeloma

Electronically Signed by Jeffrey S. Ross M.D., Medical Director | CLIA Number: 22D2027531 | Foundation Medicine, Inc., 150 2nd Street, 1st Floor, Cambridge, MA 02141 | 1.888.988.3639 page 6 of 14

CLINICAL TRIALS TO CONSIDER

IMPORTANT: While every effort is made to ensure the accuracy of the information contained below, the information available in thepublic domain is continuously updated and should be investigated by the physician or research staff. This is not meant to be acomplete list of available trials. In order to conduct a more thorough search, please go to www.clinicaltrials.gov and use the searchterms provided below. For more information about a specific clinical trial, type the NCT ID of the trial indicated below into the searchbar.

GENE RATIONALE FOR POTENTIAL CLINICAL TRIALS

IGHIGH-MMSET(WHSC1) and IGH-FGFR3rearrangement

This rearrangement may result in up-regulation of MMSET and FGFR3 expression. BET domain inhibitorshave been reported to inhibit IGH-mediated transcriptional activation for an IGH-MYC rearrangement andmay therefore be relevant here. Furthermore, FGFR3 inhibitors may be relevant in a tumor with FGFR3overexpression or activation.

However, because it is not known whether this tumor exhibits overexpression of FGFR3, it is unclear thattherapies targeting FGFR3 would be beneficial here.

Examples of clinical trials that may be appropriate for this patient are listed below. These trials wereidentified through a search of the trial website clinicaltrials.gov using keyword terms such as "Cdk4", "PD0332991", "BAY 1000394", "LEE011", "LY2835219", "BET", "BRD4", "CPI-0610", "I-BET762", "GSK525762","GSK1324726A", "TEN-010", "RVX-208", "OTX015", "FGFR", "dovitinib", "pazopanib", "ponatinib" and/or"myeloma".

TITLE PHASE TARGETS LOCATIONS NCT IDModular Phase II Study to Link TargetedTherapy to Patients With Pathway ActivatedTumors: Module 2 - Dovitinib for Patients WithTumor Pathway Activations Inhibited byDovitinib Including Tumors With Mutations orTranslocations of FGFR, PDGFR, VEGF, cKIT,FLT3, CSFR1, Trk and RET

Phase 2 FGFR,PDGFR,VEGF, KIT,FLT3,CSFR1, TRK,RET

Arkansas, California, Georgia,Illinois, Michigan, Nevada,Tennessee, Texas, Washington

NCT01831726

A Phase I, Dose-finding Study of theBromodomain (Brd) Inhibitor OTX015 inHaematological Malignancies

Phase 1 BRD2/3/4 Bellinzona (Switzerland), Lille(France), Paris (France),Torino (Italy)

NCT01713582

Patient Name Report DateTumor TypeBone marrowmultiple myeloma

Electronically Signed by Jeffrey S. Ross M.D., Medical Director | CLIA Number: 22D2027531 | Foundation Medicine, Inc., 150 2nd Street, 1st Floor, Cambridge, MA 02141 | 1.888.988.3639 page 7 of 14

APPENDIX

VARIANTS OF UNKNOWN SIGNIFICANCENote: One or more variants of unknown significance (VUS) were detected in this patient's tumor. These variants may not have beenadequately characterized in the scientific literature at the time this report was issued, and/or the genomic context of these alterationsmake their significance unclear. We choose to include them here in the event that they become clinically meaningful in the future.

ARG457_G462del

IGF1RN284Y

PTPROP318L

DNM2D270N

MUTYHL406M

SPENK1600_D1601insK

DOT1LA854T

PCLOG1369R

FLT4P1218L

PTPN11S499A

Patient Name Report DateTumor TypeBone marrowmultiple myeloma

Electronically Signed by Jeffrey S. Ross M.D., Medical Director | CLIA Number: 22D2027531 | Foundation Medicine, Inc., 150 2nd Street, 1st Floor, Cambridge, MA 02141 | 1.888.988.3639 page 8 of 14

APPENDIX

GENES ASSAYED IN FOUNDATIONONE HEME

FoundationOne Heme is designed to include all genes known to be somatically altered in human hematologic malignancies, sarcomasand pediatric cancers that are validated targets for therapy, either approved or in clinical trials, and/or that are unambiguous drivers ofoncogenesis based on current knowledge. The current assay utilizes DNA sequencing to interrogate 405 genes as well as selectedintrons of 31 genes involved in rearrangements, in addition to RNA sequencing of 265 genes. The assay will be updated periodically toreflect new knowledge about cancer biology.

DNA Gene List: Entire Coding Sequence for the Detection of Base Substitutions, Insertion/Deletions, and Copy Number Alterations

ABL1 ACTB AKT1 AKT2 AKT3 ALK AMER1 APC APH1A AR ARAF APFRP1 ARHGAP26 ARHGAP26

ARID1A ARID2 ASMTL ASXL1 ATM ATR ATRX AURKA AURKB AXIN1 AXL B2M BAP1 BAP1

BARD1 BCL10 BCL11B BCL2 BCL2L2 BCL6 BCL7A BCOR BCORL1 BIRC3 BLM BRAF BRCA1 BRCA1

BRCA2 BRD4 BRIP1 BRSK1 BTG2 BTK BTLA C11orf30 CAD CARD11 CBFB CBL CCND1 CCND1

CCND2 CCND3 CCNE1 CCT6B CD22 CD274 CD36 CD58 CD70 CD79A CD79B CDC73 CDH1 CDH1

CDK12 CDK4 CDK6 CDK8 CDKN1B CDKN2A CDKN2B CDKN2C CEBPA CHD2 CHEK1 CHEK2 CIC CIC

CIITA CKS1B CPS1 CREBBP CRKL CRLF2 CSF1R CSF3R CTCF CTNNA1 CTNNB1 CUX1 CXCR4 CXCR4

DAXX DDR2 DDX3X DNM2 DNMT3A DOT1L DTX1 DUSP2 DUSP9 EBF1 ECT2L EED EGFR EGFR

ELP2 EP300 EPHA3 EPHA5 EPHA7 EPHB1 ERBB2 ERBB3 ERBB4 ERG ESR1 ETS1 ETV6 ETV6

EXOSC6 EZH2 FAF1 FAM46C FANCA FANCC FANCD2 FANCE FANCF FANCG FANCL FAS FBXO11 FBXO11

FBXO31 FBXW7 FGF10 FGF14 FGF19 FGF23 FGF3 FGF4 FGF6 FGFR1 FGFR2 FGFR3 FGFR4 FGFR4

FHIT FLCN FLT1 FLT3 FLT4 FLYWCH1 FOXL2 FOXO1 FOXO3 FOXP1 FRS2 GADD45B GATA1 GATA1

GATA2 GATA3 GID4 GNA11 GNA12 GNA13 GNAQ GNAS GPR124 GRIN2A GSK3B GTSE1 HDAC1 HDAC1

HDAC4 HDAC7 HGF HIST1H1C HIST1H1D HIST1H1E HIST1H2AC HIST1H2AG HIST1H2AL HIST1H2AM HIST1H2BC HIST1H2BJ HIST1H2BK HIST1H2BK

HIST1H2BO HIST1H3B HNF1A HRAS HSP90AA1 ICK ID3 IDH1 IDH2 IGF1R IKBKE IKZF1 IKZF2 IKZF2

IKZF3 IL7R INHBA INPP4B INPP5D IRF1 IRF4 IRF8 IRS2 JAK1 JAK2 JAK3 JARID2 JARID2

JUN KAT6A KDM2B KDM4C KDM5A KDM5C KDM6A KDR KEAP1 KIT KLHL6 KMT2A KMT2B KMT2B

KMT2C KRAS LEF1 LRP1B LRRK2 MAF MAFB MAGED1 MALT1 MAP2K1 MAP2K2 MAP2K4 MAP3K1 MAP3K1

MAP3K14 MAP3K6 MAP3K7 MAPK1 MCL1 MDM2 MDM4 MED12 MEF2B MEF2C MEN1 MET MIB1 MIB1

MITF MKI67 MLH1 MPL MRE11A MSH2 MSH3 MSH6 MTOR MUTYH MYC MYCL MYCN MYCN

MYD88 MYO18A NCOR2 NCSTN NF1 NF2 NFE2L2 NFKBIA NKX2-1 NOD1 NOTCH1 NOTCH2 NPM1 NPM1

NRAS NT5C2 NTRK1 NTRK2 NTRK3 NUP93 NUP98 P2RY8 PAG1 PAK3 PALB2 PASK PAX5 PAX5

PBRM1 PC PCBP1 PCLO PDCD1 PDCD11 PDCD1LG2 PDGFRA PDGFRB PDK1 PHF6 PIK3CA PIK3CG PIK3CG

PIK3R1 PIK3R2 PIM1 PLCG2 POT1 PPP2R1A PRDM1 PRKAR1A PRKDC PRSS8 PTCH1 PTEN PTPN11 PTPN11

PTPN2 PTPN6 PTPRO RAD21 RAD50 RAD51 RAF1 RARA RASGEF1A RB1 RELN RET RHOA RHOA

RICTOR RNF43 ROS1 RPTOR RUNX1 S1PR2 SDHA SDHB SDHC SDHD SERP2 SETBP1 SETD2 SETD2

SF3B1 SGK1 SMAD2 SMAD4 SMARCA1 SMARCA4 SMARCB1 SMC1A SMC3 SMO SOCS1 SOCS2 SOCS3 SOCS3

SOX10 SOX2 SPEN SPOP SRC SRSF2 STAG2 STAT3 STAT4 STAT5A STAT5B STAT6 STK11 STK11

SUFU SUZ12 TAF1 TBL1XR1 TCF3 TCL1A TET2 TGFBR2 TLL2 TMEM30A TMSB4XP8 TNFAIP3 TNFRSF11A RUNX1

TNFRSF14 TNFRSF17 TOP1 TP53 TP63 TRAF2 TRAF3 TRAF5 TSC1 TSC2 TSHR TUSC3 TYK2 TUSC3

U2AF1 U2AF2 VHL WDR90 WHSC1 WISP3 WT1 XBP1 XPO1 YY1AP1 ZMYM3 ZNF217 ZNF24 ZNF217

ZNF703 ZRSR2

DNA Gene List: For the Detection of Select RearrangementsALK BCL2 BCL6 BCR BRAF CCND1 CRLF2 EGFR EPOR ETV1 ETV4 ETV5 ETV6 ETV6

EWSR1 FGFR2 IGH IGK IGL JAK1 JAK2 KMT2A MYC NTRK1 PDGFRA PDGFRB RAF1 RAF1

RARA RET ROS1 TMPRSS2 TRG

Patient Name Report DateTumor TypeBone marrowmultiple myeloma

Electronically Signed by Jeffrey S. Ross M.D., Medical Director | CLIA Number: 22D2027531 | Foundation Medicine, Inc., 150 2nd Street, 1st Floor, Cambridge, MA 02141 | 1.888.988.3639 page 9 of 14

RNA Gene List: For the Detection of Select Gene Fusions

ABI1 ABL1 ABL2 ACSL6 AFF1 AFF4 ALK ARHGAP26 ARHGEF12 ARID1A ARNT ASXL1

ATF1 ATG5 ATIC BCL10 BCL11A BCL11B BCL2 BCL3 BCL6 BCL7A BCL9 BCOR

BCR BIRC3 BRAF BTG1 CAMTA1 CARS CBFA2T3 CBFB CBL CCND1 CCND2 CCND3

CD274 CDK6 CDX2 CHIC2 CHN1 CIC CIITA CLP1 CLTC CLTCL1 CNTRL COL1A1

CREB3L1 CREB3L2 CREBBP CRLF2 CSF1 CTNNB1 DDIT3 DDX10 DDX6 DEK DUSP22 EGFR

EIF4A2 ELF4 ELL ELN EML4 EP300 EPOR EPS15 ERBB2 ERG ETS1 ETV1

ETV4 ETV5 ETV6 EWSR1 FCGR2B FCRL4 FEV FGFR1 FGFR1OP FGFR2 FGFR3 FLI1

FNBP1 FOXO1 FOXO3 FOXO4 FOXP1 FSTL3 FUS GAS7 GLI1 GMPS GPHN HERPUD1

HEY1 HIP1 HIST1H4I HLF HMGA1 HMGA2 HOXA11 HOXA13 HOXA3 HOXA9 HOXC11 HOXC13

HOXD11 HOXD13 HSP90AA1 HSP90AB1 IGH IGK IGL IKZF1 IL21R IL3 IRF4 ITK

JAK1 JAK2 JAK3 JAZF1 KAT6A KDSR KIF5B KMT2A LASP1 LCP1 LMO1 LMO2

LPP LYL1 MAF MAFB MALT1 MDS2 MECOM MKL1 MLF1 MLLT1 MLLT10 MLLT3

MLLT4 MLLT6 MN1 MNX1 MSI2 MSN MUC1 MYB MYC MYH11 MYH9 NACA

NBEAP1 NCOA2 NDRG1 NF1 NF2 NFKB2 NIN NOTCH1 NPM1 NR4A3 NSD1 NTRK1

NTRK2 NTRK3 NUMA1 NUP214 NUP98 NUTM2A OMD P2RY8 PAFAH1B2 PAX3 PAX5 PAX7

PBX1 PCM1 PCSK7 PDCD1LG2 PDE4DIP PDGFB PDGFRA PDGFRB PER1 PHF1 PICALM PIM1

PLAG1 PML POU2AF1 PPP1CB PRDM1 PRDM16 PRRX1 PSIP1 PTCH1 PTK7 RABEP1 RAF1

RALGDS RAP1GDS1 RARA RBM15 RET RHOH RNF213 ROS1 RPL22 RPN1 RUNX1 RUNX1T1

RUNX2 SEC31A SEPT5 SEPT6 SEPT9 SET SH3GL1 SLC1A2 SNX29 SRSF3 SS18 SSX1

SSX2 SSX4 STAT6 STL SYK TAF15 TAL1 TAL2 TBL1XR1 TCF3 TCL1A TEC

TET1 TFE3 TFG TFPT TFRC TLX1 TLX3 TMPRSS2 TNFRSF11A TOP1 TP63 TPM3

TPM4 TRIM24 TRIP11 TTL TYK2 USP6 WHSC1 WHSC1L1 YPEL5 ZBTB16 ZMYM2 ZNF384

ZNF521

Patient Name Report DateTumor TypeBone marrowmultiple myeloma

Electronically Signed by Jeffrey S. Ross M.D., Medical Director | CLIA Number: 22D2027531 | Foundation Medicine, Inc., 150 2nd Street, 1st Floor, Cambridge, MA 02141 | 1.888.988.3639 page 10 of 14

APPENDIX

PERFORMANCE SPECIFICATIONS

SENSITIVITY

Base Substitutions at 5% Minor Allele Frequency >99%

Insertions/Deletions (1-40 base pairs) at 10% Minor Allele Frequency 98%

Focal Copy Number Alterations (homozygous deletions or amplifications 8copies)

>95%

Known Gene Fusions >95%

SPECIFICITYPositive Predictive Value (PPV) for Base Substitutions, Insertions/Deletionsand Focal Copy Number Alterations

>99%

Positive Predictive Value (PPV) for Known Gene Fusions >95%

REPRODUCIBILITYConcordance between replicates inter-batch 97%

Concordance between replicates intra-batch 97%

Patient Name Report DateTumor TypeBone marrowmultiple myeloma

Electronically Signed by Jeffrey S. Ross M.D., Medical Director | CLIA Number: 22D2027531 | Foundation Medicine, Inc., 150 2nd Street, 1st Floor, Cambridge, MA 02141 | 1.888.988.3639 page 11 of 14

APPENDIX

REFERENCES

1 Oxelius VA, Pandey JP (2013) Human immunoglobulin constant heavy G chain (IGHG) (Fc) (GM) genes, defining innatevariants of IgG molecules and B cells, have impact on disease and therapy. Clin Immunol 149(3):475-86

2 Pinaud E, Marquet M, Fiancette R, et al. (2011) The IgH locus 3' regulatory region: pulling the strings from behind. Adv Immunol110:27-70

3 Martin LD, Belch AR, Pilarski LM (2010) Promiscuity of translocation partners in multiple myeloma. J Cell Biochem 109(6):1085-94

4 Walker BA, Wardell CP, Johnson DC, et al. (2013) Characterization of IGH locus breakpoints in multiple myeloma indicates asubset of translocations appear to occur in pregerminal center B cells. Blood 121(17):3413-9

5 Bergsagel PL, Kuehl WM (2001) Chromosome translocations in multiple myeloma. Oncogene 20(40):5611-22

6 Avet-Loiseau H, Facon T, Grosbois B, et al. (2002) Oncogenesis of multiple myeloma: 14q32 and 13q chromosomalabnormalities are not randomly distributed, but correlate with natural history, immunological features, and clinical presentation.Blood 99(6):2185-91

7 Fonseca R, Blood E, Rue M, et al. (2003) Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood101(11):4569-75

8 Nishida K, Tamura A, Nakazawa N, et al. (1997) The Ig heavy chain gene is frequently involved in chromosomal translocations inmultiple myeloma and plasma cell leukemia as detected by in situ hybridization. Blood 90(2):526-34

9 Bergsagel PL, Kuehl WM (2005) Molecular pathogenesis and a consequent classification of multiple myeloma. J Clin Oncol23(26):6333-8

10 Keats JJ, Reiman T, Maxwell CA, et al. (2003) In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespectiveof FGFR3 expression. Blood 101(4):1520-9

11 Avet-Loiseau H, Leleu X, Roussel M, et al. (2010) Bortezomib plus dexamethasone induction improves outcome of patients witht(4;14) myeloma but not outcome of patients with del(17p). J Clin Oncol 28(30):4630-4

12 Keats JJ, Reiman T, Belch AR, et al. (2006) Ten years and counting: so what do we know about t(4;14)(p16;q32) multiplemyeloma. Leuk Lymphoma 47(11):2289-300

13 Chesi M, Nardini E, Lim RS, et al. (1998) The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene,MMSET, resulting in IgH/MMSET hybrid transcripts. Blood 92(9):3025-34

14 Keats JJ, Maxwell CA, Taylor BJ, et al. (2005) Overexpression of transcripts originating from the MMSET locus characterizes allt(4;14)(p16;q32)-positive multiple myeloma patients. Blood 105(10):4060-9

15 Kim JY, Kee HJ, Choe NW, et al. (2008) Multiple-myeloma-related WHSC1/MMSET isoform RE-IIBP is a histonemethyltransferase with transcriptional repression activity. Mol Cell Biol 28(6):2023-34

16 Martinez-Garcia E, Popovic R, Min DJ, et al. (2011) The MMSET histone methyl transferase switches global histone methylationand alters gene expression in t(4;14) multiple myeloma cells. Blood 117(1):211-20

17 Pei H, Zhang L, Luo K, et al. (2011) MMSET regulates histone H4K20 methylation and 53BP1 accumulation at DNA damagesites. Nature 470(7332):124-8

18 Marango J, Shimoyama M, Nishio H, et al. (2008) The MMSET protein is a histone methyltransferase with characteristics of atranscriptional corepressor. Blood 111(6):3145-54

19 Lauring J, Abukhdeir AM, Konishi H, et al. (2008) The multiple myeloma associated MMSET gene contributes to cellularadhesion, clonogenic growth, and tumorigenicity. Blood 111(2):856-64

20 Brito JL, Walker B, Jenner M, et al. (2009) MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14)myeloma plasma cells. Haematologica 94(1):78-86

Patient Name Report DateTumor TypeBone marrowmultiple myeloma

Electronically Signed by Jeffrey S. Ross M.D., Medical Director | CLIA Number: 22D2027531 | Foundation Medicine, Inc., 150 2nd Street, 1st Floor, Cambridge, MA 02141 | 1.888.988.3639 page 12 of 14

APPENDIX

REFERENCES

21 Hudlebusch HR, Santoni-Rugiu E, Simon R, et al. (2011) The histone methyltransferase and putative oncoprotein MMSET isoverexpressed in a large variety of human tumors. Clin Cancer Res 17(9):2919-33

22 Kassambara A, Klein B, Moreaux J (2009) MMSET is overexpressed in cancers: link with tumor aggressiveness. BiochemBiophys Res Commun 379(4):840-5

23 Yang S, Zhang Y, Meng F, et al. (2013) Overexpression of multiple myeloma SET domain (MMSET) is associated with advancedtumor aggressiveness and poor prognosis in serous ovarian carcinoma. Biomarkers 18(3):257-63

24 Zhou P, Wu LL, Wu KM, et al. (2013) Overexpression of MMSET is correlation with poor prognosis in hepatocellular carcinoma.Pathol Oncol Res 19(2):303-9

25 Hudlebusch HR, Skotte J, Santoni-Rugiu E, et al. (2011) MMSET is highly expressed and associated with aggressiveness inneuroblastoma. Cancer Res 71(12):4226-35

26 Kuehl WM, Bergsagel PL (2012) Molecular pathogenesis of multiple myeloma and its premalignant precursor. J Clin Invest122(10):3456-63

27 Kalff A, Spencer A (2012) The t(4;14) translocation and FGFR3 overexpression in multiple myeloma: prognostic implications andcurrent clinical strategies. Blood Cancer J 2:e89

28 Powers CJ, McLeskey SW, Wellstein A (2000) Fibroblast growth factors, their receptors and signaling. Endocr Relat Cancer7(3):165-97

29 Karlin L, Soulier J, Chandesris O, et al. (2011) Clinical and biological features of t(4;14) multiple myeloma: a prospective study.Leuk Lymphoma 52(2):238-46

30 Ho PJ, Brown RD, Spencer A, et al. (2012) Thalidomide consolidation improves progression-free survival in myeloma with normalbut not up-regulated expression of fibroblast growth factor receptor 3: analysis from the Australasian Leukaemia and LymphomaGroup MM6 clinical trial. Leuk Lymphoma 53(9):1728-34

31 Zingone A, Cultraro CM, Shin DM, et al. (2010) Ectopic expression of wild-type FGFR3 cooperates with MYC to acceleratedevelopment of B-cell lineage neoplasms. Leukemia 24(6):1171-8

32 Li Z, Zhu YX, Plowright EE, et al. (2001) The myeloma-associated oncogene fibroblast growth factor receptor 3 is transforming inhematopoietic cells. Blood 97(8):2413-9

33 Plowright EE, Li Z, Bergsagel PL, et al. (2000) Ectopic expression of fibroblast growth factor receptor 3 promotes myeloma cellproliferation and prevents apoptosis. Blood 95(3):992-8

34 Zhu L, Somlo G, Zhou B, et al. (2005) Fibroblast growth factor receptor 3 inhibition by short hairpin RNAs leads to apoptosis inmultiple myeloma. Mol Cancer Ther 4(5):787-98

35 Delmore JE, Issa GC, Lemieux ME, et al. (2011) BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell146(6):904-17

36 Brown CJ, Lain S, Verma CS, et al. (2009) Awakening guardian angels: drugging the p53 pathway. Nat Rev Cancer 9(12):862-73

37 Joerger AC, Fersht AR (2008) Structural biology of the tumor suppressor p53. Annu Rev Biochem 77:557-82

38 Kato S, Han SY, Liu W, et al. (2003) Understanding the function-structure and function-mutation relationships of p53 tumorsuppressor protein by high-resolution missense mutation analysis. Proc Natl Acad Sci USA 100(14):8424-9

39 Kamada R, Nomura T, Anderson CW, et al. (2011) Cancer-associated p53 tetramerization domain mutants: quantitative analysisreveals a low threshold for tumor suppressor inactivation. J Biol Chem 286(1):252-8

40 Chesi M, Bergsagel PL (2011) Many multiple myelomas: making more of the molecular mayhem. Hematology Am Soc HematolEduc Program 2011:344-53

41 Avet-Loiseau H, Attal M, Moreau P, et al. (2007) Genetic abnormalities and survival in multiple myeloma: the experience of theIntergroupe Francophone du Myélome. Blood 109(8):3489-95

Patient Name Report DateTumor TypeBone marrowmultiple myeloma

Electronically Signed by Jeffrey S. Ross M.D., Medical Director | CLIA Number: 22D2027531 | Foundation Medicine, Inc., 150 2nd Street, 1st Floor, Cambridge, MA 02141 | 1.888.988.3639 page 13 of 14

APPENDIX

REFERENCES

42 Chng WJ, Price-Troska T, Gonzalez-Paz N, et al. (2007) Clinical significance of TP53 mutation in myeloma. Leukemia 21(3):582-4

43 Neri A, Baldini L, Trecca D, et al. (1993) p53 gene mutations in multiple myeloma are associated with advanced forms ofmalignancy. Blood 81(1):128-35

44 Chen MH, Qi CX, Saha MN, et al. (2012) p53 nuclear expression correlates with hemizygous TP53 deletion and predicts anadverse outcome for patients with relapsed/refractory multiple myeloma treated with lenalidomide. Am J Clin Pathol 137(2):208-12

45 Boyd KD, Ross FM, Tapper WJ, et al. (2011) The clinical impact and molecular biology of del(17p) in multiple myeloma treatedwith conventional or thalidomide-based therapy. Genes Chromosomes Cancer 50(10):765-74

46 Avet-Loiseau H, Li JY, Godon C, et al. (1999) P53 deletion is not a frequent event in multiple myeloma. Br J Haematol 106(3):717-9

47 Tiedemann RE, Gonzalez-Paz N, Kyle RA, et al. (2008) Genetic aberrations and survival in plasma cell leukemia. Leukemia22(5):1044-52

48 Chang H, Sloan S, Li D, et al. (2005) Genomic aberrations in plasma cell leukemia shown by interphase fluorescence in situhybridization. Cancer Genet Cytogenet 156(2):150-3

49 Sorrell AD, Espenschied CR, Culver JO, et al. (2013) Tumor protein p53 (TP53) testing and Li-Fraumeni syndrome : currentstatus of clinical applications and future directions. Mol Diagn Ther 17(1):31-47

50 Nichols KE, Malkin D, Garber JE, et al. (2001) Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers.Cancer Epidemiol Biomarkers Prev 10(2):83-7

51 Lalloo F, Varley J, Ellis D, et al. (2003) Prediction of pathogenic mutations in patients with early-onset breast cancer by familyhistory. Lancet 361(9363):1101-2

52 Gonzalez KD, Noltner KA, Buzin CH, et al. (2009) Beyond Li Fraumeni Syndrome: clinical characteristics of families with p53germline mutations. J Clin Oncol 27(8):1250-6

53 Saha MN, Micallef J, Qiu L, et al. (2010) Pharmacological activation of the p53 pathway in haematological malignancies. J ClinPathol 63(3):204-9

54 Prince HM, Hönemann D, Spencer A, et al. (2009) Vascular endothelial growth factor inhibition is not an effective therapeuticstrategy for relapsed or refractory multiple myeloma: a phase 2 study of pazopanib (GW786034). Blood 113(19):4819-20

55 Gozgit JM, Wong MJ, Moran L, et al. (2012) Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multipleFGFR-amplified or mutated cancer models. Mol Cancer Ther 11(3):690-9

56 Traer E, Javidi-Sharifi N, Agarwal A, et al. (2014) Ponatinib overcomes FGF2-mediated resistance in CML patients without kinasedomain mutations. Blood ePub Jan 2014

Patient Name Report DateTumor TypeBone marrowmultiple myeloma

Electronically Signed by Jeffrey S. Ross M.D., Medical Director | CLIA Number: 22D2027531 | Foundation Medicine, Inc., 150 2nd Street, 1st Floor, Cambridge, MA 02141 | 1.888.988.3639 page 14 of 14

APPENDIX

ABOUT THE TEST

FoundationOne Heme: FoundationOne Heme (the Test) was developed and its performance characteristics determined byFoundation Medicine, Inc. (Foundation Medicine). The Test has not been cleared or approved by the United States Food and DrugAdministration (FDA). The FDA has determined that such clearance or approval is not necessary. The Test may be used for clinicalpurposes and should not be regarded as purely investigational or for research only. Foundation Medicine’s clinical referencelaboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) as qualified to perform high-complexity clinical testing.

Diagnostic Significance: FoundationOne Heme identifies alterations to select cancer-associated genes or portions of genes(biomarkers). In some cases, the Test Report also highlights selected negative test results regarding biomarkers of clinicalsignificance.

Qualified Alteration Calls (Equivocal and Subclonal): An alteration denoted as “amplification – equivocal” implies thatFoundationOne Heme data provide some, but not unambiguous, evidence that the copy number of a gene exceeds the threshold foridentifying copy number amplification. The threshold used in FoundationOne Heme for identifying a copy number amplification isfive (5) for ERBB2 and six (6) for all other genes. Conversely, an alteration denoted as “loss – equivocal” implies thatFoundationOne Heme data provide some, but not unambiguous, evidence for homozygous deletion of the gene in question. Analteration denoted as “subclonal” is one that FoundationOne Heme analytical methodology has identified as being present in <10%of the assayed tumor DNA.

The Report incorporates analyses of peer-reviewed studies and other publicly available information indentified by FoundationMedicine; these analyses and information may include associations between a molecular alteration (or lack of alteration) and one ormore drugs with potential clinical benefit (or potential lack of clinical benefit), including drug candidates that are being studied inclinical research.

NOTE: A finding of biomarker alteration does not necessarily indicate pharmacologic effectiveness (or lack thereof) of any drug ortreatment regimen; a finding of no biomarker alteration does not necessarily indicate lack of pharmacologic effectiveness (oreffectiveness) of any drug or treatment regimen.

Alterations and Drugs Not Presented in Ranked Order: In this Report, neither any biomarker alteration, nor any drug associatedwith potential clinical benefit (or potential lack of clinical benefit), are ranked in order of potential or predicted efficacy.

Level of Evidence Not Provided: Drugs with potential clinical benefit (or potential lack of clinical benefit) are not evaluated forsource or level of published evidence.

No Guarantee of Clinical Benefit: This Report makes no promises or guarantees that a particular drug will be effective in thetreatment of disease in any patient. This Report also makes no promises or guarantees that a drug with potential lack of clinicalbenefit will in fact provide no clinical benefit.

No Guarantee of Reimbursement: Foundation Medicine makes no promises or guarantees that a healthcare provider, insurer orother third party payor, whether private or governmental, will reimburse a patient for the cost of the Test.

Treatment Decisions are Responsibility of Physician: Drugs referenced in this Report may not be suitable for a particularpatient. The selection of any, all or none of the drugs associated with potential clinical benefit (or potential lack of clinical benefit)resides entirely within the discretion of the treating physician. Indeed, the information in this Report must be considered inconjunction with all other relevant information regarding a particular patient, before the patient’s treating physician recommends acourse of treatment.

Decisions on patient care and treatment must be based on the independent medical judgment of the treating physician, taking intoconsideration all applicable information concerning the patient’s condition, such as patient and family history, physical examinations,information from other diagnostic tests, and patient preferences, in accordance with the standard of care in a given community. Atreating physician’s decisions should not be based on a single test, such as this Test, or the information contained in this Report.

Certain sample or variant characteristics may result in reduced sensitivity. These include: subclonal alterations in heterogeneoussamples, low sample quality or with homozygous losses of <3 exons; and deletions and insertions >40bp, or in repetitive/highhomology sequences. FoundationOne Heme is performed using DNA and RNA derived from tumor, and as such germline eventsmay not be reported.