In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e17119-e17119
Abstract:
e17119 Background: Inherited mutations (muts) in Lynch Syndrome genes (LS) & PTEN are associated with EC. The prevalence of other cancer predisposition genes is unclear. The majority of studies have selected pts by age, family history or specific tumor features. We sought the prevalence of cancer predisposition genes in unselected pts attending for surgical consultation. Methods: 03/2016-10/2016, pts with new EC diagnosis were offered to consent to an IRB approved protocol. Tumor-normal sequencing, was performed via a custom next-generation sequencing panel (MSK-IMPACT) with return of results for 76 cancer predisposition genes. Per institutional standard, all ECs undergo reflex screening for LS with IHC for mismatch repair proteins (MMR P). Results:77 pts consented, median age 60 (27-84), median BMI 27 (16-66), 27% Ashkenazi Jewish (AJ) descent. Tumors: 56 (73%) stage 1, remainder stage 3 or 4, majority (52, 68%) endometrioid histology, of which 31 (60%) grade 1. 15 pathogenic germline variants were identified in 14 pts (18%) including 3 (4%) in LS genes (2 MSH6, 1 MLH1) with corresponding abnormal MMR P. One pt with a known BRCA1 mutation, without prior cancer, with prior risk reducing salpingo-oophorectomy had stage III grade 3 endometrioid EC at 47 yo, tumor LOH at BRCA1 was identified. Of the 4 pts with high-penetrance muts, 3 met criteria for genetic testing for the implicated gene due to personal/family cancer history, 1 pt with MSH6 mutation was identified via absent MMR P only. The remaining 11 pathogenic variants were incremental findings in moderate penetrance ( CHEK2 I157T, MRE11, ATM, APC I1307K, MUTYH) or autosomal recessive genes ( MUTYH, RECQL4, ATM). 5 pt had moderate penetrance variants in known AJ founder muts. Conclusions: In this cohort of unselected EC pts the prevalence of LS was as expected & reflex IHC screening captured all pts appropriately. While all high-penetrance muts were captured by clinical criteria, the incremental identification of moderate penetrance muts in these largely early stage/ low risk EC pts may alter personal & at-risk family member breast & colon cancer screening recommendations. Continuing accrual will reveal the extent to which additional high penetrance genes are seen in unselected EC pts.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.15_suppl.e17119
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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