GASTRIC CANCERGastric cancer, also known as stomach cancer, refers to cancers originating from cells in the stomach lining. There are several factors that may increase your risk of stomach cancer, including: [1]

• Having a chronic stomach condition, such as Helicobacter pylori (H. pylori) infection, chronic gastritis and gastric polyps

• A diet high in salty and smoked foods, and low in fruit and vegetables

• Tobacco smoking• A family history of stomach cancer

Although majority of gastric cancers are associated with infectious agents, a small number are associated with inherited mutations. Molecular analysis of gastric cancers has identified four major genomic subtypes: [2]

• Tumours positive for Epstein–Barr virus (EBV)• Microsatellite unstable (MSI) tumours• Genomically stable tumours• Chromosomally unstable tumours

How can genomic testing benefit me?

Focusing on Personalised Medicine

The power of genomic testing in Gastric Cancer

Although Gastric Cancers all arise from stomach cells, there are many different genetic drivers of the cancer, meaning that a detailed genetic analysis is important for choosing the most effective treatment plan. Genomic alterations have been reported in a number of genes in Gastric Cancer including TP53, ARID1A and RNF43.[3]

TP53 is the most frequently mutated gene in gastric carcinoma, occuring in ~50% of cases. [4] The most predominant class of genes frequently amplified in gastric carcinomas are those related to RTK/RAS/MAPK signalling, including HER2, EGFR, MET, FGFR2, KRAS and NRAS genes.[4] In total, about 30%-40% of gastric carcinomas are likely to harbor a RTK/RAS/MAPK-related amplification. [4] Other gene amplifications in gastric carcinomas are related to cell cycle control, including CCND1, CCNE1 and CDK6. [4] Genomic deletions also frequently occur in gastric carcinoma, involving tumour suppressor genes such as CDKN2A/B. [4]

Clinical trials have shown that personalised therapies, developed from genetic testing of tumours, are the most effective way to improve treatment outcomes. Patients undertaking therapy as a result from genetic testing are shown to have longer progression-free, higher response rates to treatment and overall greater survival rates. [5-7] Investing in genomic testing to obtain a complete and accurate diagnosis, is small compared to the time and money that may be wasted on generic or ill-chosen therapies. Genomic testing provides a powerful diagnostic tool, and every patient deserves an accurate diagnosis.

Depending on the type of testing done, a comprehensive genomic analysis may provide information on potential therapeutics, development of resistance to treatments, prognosis and disease tracking, and may provide access to clinical trials and new treatments. Genomic sequencing of your gastric cancer may identify:

• CCNE1 amplifications, which often occur together with HER-2 amplification and lead to resistance of HER-2 targeted therapies such as Tratsuzmab, providing answers when the cancer may have progressed. [8]

• ARID1A mutations, which sensitizes cancer cells to PARP inhibitors, providing a potential therapeutic strategy for patients with ARID1A-mutant tumours. [9]

• CCND1 mutations which may have a negative prognostic role in gastric cancer. [10]

• Many other mutations in 161 genes* that will help guide your treatment by highlighting potential drug targets, drug resistance or prognosis, as a small percentage of tumours will have rare mutations that may be associated with specific targeted therapy.

*When choosing our OncomineTM Solid Tumour Analysis

Toll Free: 1800 445 433 Fax: 1300 658 893 Email: patientcare@genomicsforlife.com.au Web: www.genomicsforlife.com.au

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What testing options are available to me?

OncomineTM Solid Tumour Analysis • The OncomineTM Solid Tumour Analysis is a comprehensive cancer panel that may detect DNA mutations and RNA fusions

across 161 genes that are commonly indicated in a range of cancer types.• Some of the most commonly mutated genes found in gastric cancers include TP53, ARID1A, RNF43, HER2, EGFR, MET, FGFR2,

KRAS, NRAS, CCND1, CCNE1, CDK6, CDKN2A and CDKN2B, all of which are covered by this test. • Your personalised report will provide you with the genetic characteristics of your tumour, which may provide information on po-

tential therapeutics, resistance to therapeutics, prognosis and clinical trials or new treatments you may be able to access.• This analysis also covers Copy Number Variations and Tumour Mutational Burden, which can indicate your likel response to

Immune Checkpoint Inhibitors.

Cell-Free Tumour DNA (ctDNA) Testing and Tracking • Tumours may release small fragments of DNA (ctDNA) into the blood stream, which may contain identical mutations to those

identified in the primary tumour. • Our Cell-Free Pan Cancer Assay covers 52 genes commonly found in a range of cancers, including: TP53, HER2, EGFR, MET,

FGFR2, KRAS, NRAS, CCND1 and CDK6.• ctDNA can be tracked over time to monitor response to treatment and development of resistance to treatment. ctDNA testing

can also be used to check for residual cancer following treatment and accurately reflect tumour size and burden.

Pharmacogenomics (Pgx) • Multiple genes determine how drugs are metabolised in the body. Each individual has a unique genetic make-up, and therefore

will respond differently to drugs. Knowing how you will metabolise certain drugs may reduce adverse side effects, help determine optimal dosages and identify which treatments will not be effective.

• Our Pharmacogenomics test covers over 60 common oncology drugs and may assist with determining the optimal drug dose for oncology drugs and targeted therapies, and the risk of adverse reactions, helping your healthcare provider choose the most beneficial treatments for you.

Focusing on Personalised Medicine

How do I organise testing?

Genomics For Life aims to educate patients and their families on their cancer type and empower them with the knowledge to take control of their treatment plans. As each patient’s case is unique, there is no “one size fits all” when it comes to testing. We encourage you to contact Genomics For Life, and we can work with you and your oncologist/specialist, to determine what tests would benefit you.

References

1. Cancer Australia. (2019). What are the risk factors for stomach cancer? | Stomach cancer. Retreieved from https://stomach-cancer.canceraustralia.gov.au/risk-factors2. Bass, A. J., V. Thorsson, I. Shmulevich, S. M. Reynolds, M. Miller, B. Bernard, T. Hinoue, P. W. Laird, C. Curtis and H. Shen (2014). “Comprehensive molecular characterization of gastric adenocarcinoma.” Nature 513(7517): 202-209.3. Wang, K., S. T. Yuen, J. Xu, S. P. Lee, H. H. Yan, S. T. Shi, H. C. Siu, S. Deng, K. M. Chu, S. Law, K. H. Chan, A. S. Chan, W. Y. Tsui, S. L. Ho, A. K. Chan, J. L. Man, V. Foglizzo, M. K. Ng, A. S. Chan, Y. P. Ching, G. H. Cheng, T. Xie, J. Fernandez, V. S. Li, H. Clevers, P. A. Rejto, M. Mao and S. Y. Leung (2014). “Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer.” Nat Genet 46(6): 573-582.4. Tan, P. and K. G. Yeoh (2015). “Genetics and Molecular Pathogenesis of Gastric Adenocarcinoma.” Gastroenterology 149(5): 1153-1162 e1153.5. Jardim, D. L., M. Schwaederle, C. Wei, J. J. Lee, D. S. Hong, A. M. Eggermont, R. L. Schilsky, J. Mendelsohn, V. Lazar and R. Kurzrock (2015). “Impact of a Biomarker-Based Strategy on Oncology Drug Development: A Meta-analysis of Clinical Trials Leading to FDA Approval.” J Natl Cancer Inst 107(11).6. Schwaederle, M., M. Zhao, J. J. Lee, A. M. Eggermont, R. L. Schilsky, J. Mendelsohn, V. Lazar and R. Kurzrock (2015). “Impact of Precision Medicine in Diverse Cancers: A Meta-Analysis of Phase II Clinical Trials.” J Clin Oncol 33(32): 3817-38257. Subbiah, V. and R. Kurzrock (2016). “Universal genomic testing needed to win the war against cancer: Genomics is the diagnosis.” JAMA Oncology 2(6): 719-7208. Lee, J. Y., M. Hong, S. T. Kim, S. H. Park, W. K. Kang, K. M. Kim and J. Lee (2015). “The impact of concomitant genomic alterations on treatment outcome for trastuzumab therapy in HER2-positive gastric cancer.” Sci Rep 5: 9289.9. Shen, J., Y. Peng, L. Wei, W. Zhang, L. Yang, L. Lan, P. Kapoor, Z. Ju, Q. Mo, M. Shih Ie, I. P. Uray, X. Wu, P. H. Brown, X. Shen, G. B. Mills and G. Peng (2015). “ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors.” Cancer Discov 5(7): 752-767.10. Minarikova, P., L. Benesova, T. Halkova, B. Belsanova, I. Tuckova, F. Belina, L. Dusek, M. Zavoral and M. Minarik (2016). “Prognostic Importance of Cell Cycle Regulators Cyclin D1 (CCND1) and Cyclin-Dependent Kinase Inhibitor 1B (CD-KN1B/p27) in Sporadic Gastric Cancers.” Gastroenterol Res Pract 2016: 9408190.