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Abstract 3428: The landscape of germline mutations in Chinese patients with solid tumor

Background: Germline mutations harbored by cancer patients can be passed from parents on to offspring, which increases the tumor risk in offspring as well. Therefore, investigating the germline mutations in cancer patients has important clinical implications for treatment selection and familial cancer risk assessment. Methods: FFPE tumor and matched blood samples were collected from 3645 Chinese patients with solid tumors for next generation sequencing analysis. The NGS panel targeted 450 cancer genes, 47 of these genes were tumor inheritance susceptibility genes that were mentioned by NCCN guidelines. Genomic alterations including single nucleotide variations (SNV), short and long insertions/deletions (Indel), copy number variations (CNV) and gene rearrangements and fusions were assessed. Results:Germline mutations were identified in 241 of 3645 Chinese patients with solid tumor (6.6%). The patients with germline mutations included 137 males and 104 females with a median age of 54. Tumor types with higher frequency of germline mutations were: ovarian cancer (22.0%), breast cancer (13.4%), pancreatic cancer (9.9%), cholangiocarcinoma (8.6%), small intestinal cancer (8.6%), colorectal cancer (8.6%), soft tissue sarcoma (6.3%), uterine Cancer (5.9%), gastric cancer (5.8%) and bone cancer (5.1%). The distribution of germline mutations were 14.1% in BRCA1, 13.7% in BRCA2, 10.8% in SPINK1, 9.1% in ATM, 5.8% in RAD50, 4.6% in PALB2, 3.7% in BARD1 and FANCA, 3.3% in MSH6 and 2.9% in MLH1, respectively. The types of germline mutations were SNVs and short Indels, but no long Indels, CNV, gene rearrangements or fusions were observed. The percentage of patients with a family history was 27.4%, without family history was 52.7%, unknown was 19.9%. Conclusions:Our data revealed that germline mutations occurred in 6.6% of Chinese solid tumor patients. Gynecological tumor, gastrointestinal tumor, bone and soft tissue tumor are the most common types of tumors that harbored germline mutations. The most common mutant genes were HRD (64.5%) and MMR (10.5%) related genes. More than 50% patients with germline mutations had no family history, which suggests the importance of germline mutations detection for all solid tumor patients to verify if there is a risk of genetic transmission to offspring. NGS based panel sequencing showed the advantage of identifying solid tumor patients with germline mutations, and provided the information of familial cancer risk assessment and guided the precise cancer treatment options. Citation Format: Juming Li, Yongzhong Wei, Xiaoqian Chen, Angen Liu, Junping Shi, Jinwei Hu, Ming Yao. The landscape of germline mutations in Chinese patients with solid tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3428.