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www.thelancet.com/oncology Vol 14 March 2013 e90

New test predicts BRCA1 and BRCA2 mutationsA test for multigene expression profi les can detect BRCA1 or BRCA2 muta tions in otherwise healthy women, according to results that could lead to a new way to detect women at high risk of breast cancer.

Roughly 5% of breast cancers are due to an inherited mutation in BRCA1 or BRCA2. Women with such mutations have a sig nifi cantly increased risk of breast or ovarian cancer, often at an early age. Detection of the mutations can target women who would benefi t from prevention measures.

“The current tool for mutation detection is gene sequencing, which is expensive and time consuming. In many cases when it identifi es a mutation we do not know if it is neutral or harmful”, said lead author Asher Salmon (Hadassah Hebrew University Medi cal Center, Jerusalem, Israel).

Cells with mutations in BRCA1 or BRCA2 have a distinct gene expression

profi le when exposed to causes of DNA damage. The group cultured white blood cells from nine healthy women with a mutated BRCA1 gene and eight with a mutated BRCA2 gene, then exposed the cells to radiation. RNA was extracted and compared with RNA from identically treated white cells from 10 non-carriers. 1500 genes were diff erentially expressed between carriers and non-carriers. They then did a validation study with 18 of the genes that diff ered most substantially between the two groups to predict the risk of carrying a mutation in 40 women with mutations in BRCA1, BRCA2, or both, and 17 non-carriers. The test had a sensitivity of 95% and specifi city of 88% and will be assessed in a larger validation study.

“This test can serve as an aff ordable and quick prediction and screening tool for BRCA1 or BRCA2 mutation carriers

using easily obtained lymphocytes”, concluded Salmon.

Douglas Easton, professor of genetic epidemiology at the University of Cambridge, UK, said, “The paper extends work showing that breast cancers with BRCA1/2 mutations have distinct characteristics. This has been shown for BRCA1 carriers and this study fi nds a distinct expression profi le for BRCA2 carriers as well. Moreover, the diff erential ex-pression after irradiation appears to be specifi cally linked to genes in DNA damage response pathways.” He was less convinced of the clini cal application of the new test, noting that: “BRCA1/2 testing is now a routine part of clinical genetics world-wide, costs have greatly decreased, it is extremely accurate, and detects most mutations.”

Susan Mayor

Diagnostic accuracy of smartphone applicationsPeople who rely on smartphone applications to detect melanoma greatly risk misdiagnosis, according to a new study from the University of Pittsburgh. The researchers used 188 pre-existing photographs of lesions (60 melanomas and 128 benign) to examine four appli-cations. They reported that three “incorrectly classifi ed 30% or more of melanomas as unconcerning”.

Online stores have thousands of health-care applications. Those that claim to detect melanoma tend to use pattern recognition software and mathematical algorithms: an uploaded image is compared with those in the application’s database and an evaluation returned on its potential for malig-nancy. The Pittsburgh study did note a sensitivity of 98% in one application, but this one worked by sending the photograph to a

“board-certifi ed dermatologist” who issues a risk assessment roughly 24 h after receipt, which amounts to teledermatology. For the three applications in which photographs were not examined by an expert, sensitivity was 6·8%, 69%, and 70%.

This fi nding is worrying, explains co-author Laura Ferris. “Almost half of melanomas are originally identifi ed by the patient; if you see it and you’re falsely reassured that it is nothing so you don’t act, then it will grow and metastasise and become deadly.” Furthermore, a patient might have several lesions, but select one of the harmless ones to be assessed, ignoring a true malignancy that would go undetected without a physician’s examination.

Julia Newton-Bishop (Leeds University, Leeds, UK) notes the substantial invest ment in computer systems that aim to improve

melanoma recognition. But the endeavour has not yet proved successful. “Whether in the end this technology can be used to deliver a sensitive but relatively specifi c test remains to be seen”, she told The Lancet Oncology.

Smartphone applications could off er considerable benefi ts: they are inexpensive and speedy; can improve diagnosis for those in remote regions; and can assist derma-tologists in triaging patients. “But they have to be validated in a study”, stressed Ferris. She points out that America’s market for health-care applications is largely unregulated. “These applications can be sold without data to show they are accurate and without warnings of the important consequences of a late diagnosis of melanoma.”

Talha Khan Burki

Published OnlineJanuary 25, 2013 http://dx.doi.org/10.1016/S1470-2045(13)70004-4

For the study see Cancer Prev 2013; published online Jan 22. DOI:10.1158/1940-6207.CAPR-12-0105

Published OnlineJanuary 25, 2013 http://dx.doi.org/10.1016/S1470-2045(13)70003-2

For the Pittsburgh study see JAMA Dermatol 2013; published online Jan 16. DOI:10.1001/jamadermatol.2013.2382

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