Abstract 3205
Background
The prevalence of cancer related germline mutations in unselected Chinese breast cancer (BC) patients is unknown. Our study aims to examine the germline mutations prevalence and to investigate the relationship among tumor characteristics, somatic mutations and germline mutations.
Methods
Matched white blood cells and tumor tissue samples of 524 unselected Chinese BC patients (stage Tis to IV) were profiled using a panel consisting of 520 cancer-related genes. Germline mutations of 62 cancer susceptibility genes included all breast/ovarian cancer-related genes in the US genetic guidelines were assessed.
Results
A total of 76 pathogenic or likely pathogenic (P/LP) germline variants spanning 15 genes were detected from 58 patients (11%), with 29 and 38 mutations detected in BRCA1/2 and other cancer susceptibility genes, respectively. Overall, mutations detected included 11 BRCA1, 18 BRCA2, 4 MUTYH, 4 PALB2, 3 ATM, 3 BRIP1, 3 CDH1, 3 RAD51C, 2 CHEK2, 2 FANCA, 2 PMS2, 2 TP53, 1 FANCI, 1 FANCL and 1 PTEN. We detected 1968 germline mutations classified as variants of uncertain significance spanning all 62 cancer susceptibility genes from 490 patients (93%). We revealed young age, premenopausal status, and family history of breast/ovarian cancer were associated with P/LP germline mutations. Interestingly, somatic TP53 mutations were detected in all patients with P/LP germline BRCA1 mutations (100%, 11/11) and a majority (67%, 2/3) of patients with likely pathogenic CDH1 mutations. No somatic TP53 mutation was detected in patients with germline ATM and TP53 mutations. Somatic PIK3CA mutations were more frequently seen in patients with germline CDH1 (3/3). A patient with pathogenic germline PALB2 mutation (p.Q921fs) also has somatic PALB2 mutation (p.D525fs).
Conclusions
Our study derived the prevalence of P/LP germline mutation in 524 Chinese BC patients and 11% were found to have a germline mutation. We explored the characteristics of tumor somatic mutations in germline mutations carriers, which provided a better understanding of patients with germline mutations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Ning Liao.
Funding
National Natural Science Foundation of China (Grant No. 81602645), Guangdong Provincial Natural Science Foundation (Grant No. 2016A030313768).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5489 - Local immune status in cancer cell nests can be a predictor of survival for rectal cancer with neoadjuvant radiotherapy
Presenter: xijin lin
Session: Poster Display session 2
Resources:
Abstract
1653 - Impact of concomitant medications on disease free survival (DFS) and overall survival (OS) in patients from the PETACC8 study.
Presenter: Clémence Brun
Session: Poster Display session 2
Resources:
Abstract
5206 - Updated results of NORDIC 8, a randomised trial of cetuximab every 2 weeks with FOLFIRI or cetuximab with alternating FOLFIRI/FOLFOX in patients with RAS and BRAF wild type metastatic colorectal cancer.
Presenter: Per Pfeiffer
Session: Poster Display session 2
Resources:
Abstract
2992 - Clinical impact of mucinous and poorly differentiated tumors on the outcome of patients with stage II colon cancer: a TOSCA subgroup analysis
Presenter: Gerardo Rosati
Session: Poster Display session 2
Resources:
Abstract
4753 - Exercise improved adjuvant treatment completion rates and treatment-related toxicities in colorectal cancer: A prospective pilot study
Presenter: Hong Jun Kim
Session: Poster Display session 2
Resources:
Abstract
2735 - Bevacizumab plus Oxaliplatin-Based Chemotherapy as Adjuvant Treatment for Colon Cancer (CC): Updated analysis of stage II disease from the AVANT Phase III Randomized trial by the GERCOR Group
Presenter: Aimery De Gramont
Session: Poster Display session 2
Resources:
Abstract
1843 - Multicenter Validation of the Postoperative Carcinoembryonic Antigen Combined Prognostic Model for Stage Ⅲ Colon Cancer
Presenter: Ji Zhu
Session: Poster Display session 2
Resources:
Abstract
2554 - Impact of the IDEA study on clinical practice for stage III colon cancer patients: a French GERCOR - FFCD - GI UNICANCER national survey.
Presenter: Kaissa Ouali
Session: Poster Display session 2
Resources:
Abstract
3285 - Sex hormones and sperm parameters after adjuvant oxaliplatin-based treatment for colorectal cancer
Presenter: Philip Falk
Session: Poster Display session 2
Resources:
Abstract
3905 - Loss of CDX-2 expression is an independent poor prognostic biomarker in colorectal cancer
Presenter: Krittiya Korphaisarn
Session: Poster Display session 2
Resources:
Abstract