Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next‐generation sequencing with a 25‐gene panel. Issue 1 (3rd September 2014)

• Record Type: Journal Article
• Authors: Tung, Nadine; Battelli, Chiara; Allen, Brian; Kaldate, Rajesh; Bhatnagar, Satish; Bowles, Karla; Timms, Kirsten; Garber, Judy E.; Herold, Christina; Ellisen, Leif; Krejdovsky, Jill; DeLeonardis, Kim; Sedgwick, Kristin; Soltis, Kathleen; Roa, Benjamin; Wenstrup, Richard J.; Hartman, Anne‐Renee
• Is Part Of: Cancer. Volume 121:Issue 1(2015)
• Page Start: 25
• Page End: 33
• Publication Date: 2014-09-03
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.29010
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr29010-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Next‐generation sequencing (NGS) allows for simultaneous sequencing of multiple cancer susceptibility genes and, for an individual, may be more efficient and less expensive than sequential testing. The authors assessed the frequency of deleterious germline mutations among individuals with breast cancer who were referred for <italic>BRCA1</italic> and <italic>BRCA2</italic> (<italic>BRCA1/2</italic>) gene testing using a panel of 25 genes associated with inherited cancer predisposition.</p> </sec> <sec id="cncr29010-sec-0002" sec-type="section"> <title>METHODS</title> <p>This was a cross‐sectional study using NGS in 2158 individuals, including 1781 who were referred for commercial <italic>BRCA1/2</italic> gene testing (cohort 1) and 377 who had detailed personal and family history and had previously tested negative for <italic>BRCA1/2</italic> mutations (cohort 2).</p> </sec> <sec id="cncr29010-sec-0003" sec-type="section"> <title>RESULTS</title> <p>Mutations were identified in 16 genes, most frequently in <italic>BRCA1</italic>, <italic>BRCA2</italic>, <italic>CHEK2</italic>, <italic>ATM</italic>, and <italic>PALB2</italic>. Among the participants in cohort 1, 9.3% carried a <italic>BRCA1/2</italic> mutation, 3.9% carried a mutation in another breast/ovarian cancer susceptibility gene, and 0.3% carried an incidental mutation in another cancer susceptibility gene unrelated to breast or ovarian cancer. In cohort 2, the frequency of mutations in breast/ovarian‐associated genes other than <italic>BRCA1/2</italic> was 2.9%, and an additional 0.8% had an incidental mutation. In cohort 1, Lynch syndrome‐related mutations were identified in 7 individuals. In contrast to <italic>BRCA1/2</italic> mutations, neither age at breast cancer diagnosis nor family history of ovarian or young breast cancer predicted for other mutations. The frequency of mutations in genes other than <italic>BRCA1/2</italic> was lower in Ashkenazi Jews compared with non‐Ashkenazi individuals (<italic>P</italic>=.026).</p> </sec> <sec id="cncr29010-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>Using an NGS 25‐gene panel, the frequency of mutations in genes other than <italic>BRCA1/2</italic> was 4.3%, and most mutations (3.9%) were identified in genes associated with breast/ovarian cancer. <bold><italic>Cancer</italic> 2015;121:25–33</bold>. © <italic>2014 American Cancer Society</italic>.</p> </sec> </abstract>