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. 2015 Aug;17(8):630-8.
doi: 10.1038/gim.2014.176. Epub 2014 Dec 11.

V体育ios版 - Prevalence of mutations in a panel of breast cancer susceptibility genes in BRCA1/2-negative patients with early-onset breast cancer

Kara N Maxwell  1 , Bradley Wubbenhorst  2 , Kurt D'Andrea  2 , Bradley Garman  2 , Jessica M Long  1 , Jacquelyn Powers  1 , Katherine Rathbun  2 , Jill E Stopfer  1 , Jiajun Zhu  2 , Angela R Bradbury  3 , Michael S Simon  4 , Angela DeMichele  3 , Susan M Domchek  3 , Katherine L Nathanson  5
Affiliations

Prevalence of mutations in a panel of breast cancer susceptibility genes in BRCA1/2-negative patients with early-onset breast cancer

Kara N Maxwell (V体育官网) et al. Genet Med. 2015 Aug.

Abstract

Purpose: Clinical testing for germ-line variation in multiple cancer susceptibility genes is available using massively parallel sequencing. Limited information is available for pretest genetic counseling regarding the spectrum of mutations and variants of uncertain significance in defined patient populations VSports手机版. .

Methods: We performed massively parallel sequencing using targeted capture of 22 cancer susceptibility genes in 278 BRCA1/2-negative patients with early-onset breast cancer (diagnosed at younger than 40 years of age) V体育安卓版. .

Results: Thirty-one patients (11%) were found to have at least one deleterious or likely deleterious variant. Seven patients (2. 5% overall) were found to have deleterious or likely deleterious variants in genes for which clinical guidelines exist for management, namely TP53 (4), CDKN2A (1), MSH2 (1), and MUTYH (double heterozygote). Twenty-four patients (8. 6%) had deleterious or likely deleterious variants in a cancer susceptibility gene for which clinical guidelines are lacking, such as CHEK2 and ATM. Fifty-four patients (19%) had at least one variant of uncertain significance, and six patients were heterozygous for a variant in MUTYH V体育ios版. .

Conclusion: These data demonstrate that massively parallel sequencing identifies reportable variants in known cancer susceptibility genes in more than 30% of patients with early-onset breast cancer. However, only few patients (2. 5%) have definitively actionable mutations given current clinical management guidelines VSports最新版本. Genet Med 17 8, 630-638. .

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Figures

Figure 1
Figure 1. Variants identified by multiplex panel testing of 278 patients with early onset breast cancer
Germline DNA from 278 BRCA1/2 negative patients with early onset breast cancer (early-onset breast cancer) was isolated and subjected to massively parallel sequencing using a custom capture for the indicated genes in Bin A and Bin B. Sequencing data was analyzed with a custom bioinformatics pipeline and deleterious variants were called into classes (D = Deleterious, LD = Likely Deleterious, VUS = Variant of Uncertain Significance, LB = Likely Benign, and B = Benign). Inset: Proportion of patients self-reported as “White” or “Non-white” with deleterious or likely deleterious variants, VUSs only, or no reportable deleterious or likely deleterious variants or VUSs. The MUTYH heterozygous carriers included three patients heterozygous for a deleterious variant and three patients heterozygous for a VUS.
Figure 2
Figure 2. Representative family histories and sequencing data for three probands with identified mutations
A. Patient 5129, TP53 c.451C>A, p.P151T found by massively parallel sequencing and confirmed by Sanger sequencing. B. Patient 1723, TP53 c.733G>A, p.G245S found by massively parallel sequencing and confirmed by Sanger sequencing. C. Patient 5066, ATM c.8266A>T p.K2756X and CHEK2 c.444+1G>A found by massively parallel sequencing and confirmed by Sanger sequencing in both the proband and her brother (arrows).
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V体育官网入口 - References

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