Abstract 4161: Germline mutational profileof Chinese patients with colorectal cancer and diagnosed lower than 70 years
Authors: Wang Feng , Zhao Qi , Jiang Teng-jia , Wang Ying-nan , Liu Fu-rong , Hu Jia-jia , Ding Pei-rong , Pan Zhi-zhong , Shao Jian-yong , Xu Rui-hua 
Published: August 2019

Abstract
Background/Aims: Colorectal cancer (CRC) is a common cancer worldwide with increasing morbidity in China. Approximately 5% CRC are caused by well-defined hereditary CRC syndromes, whose inherited susceptibility account for nearly one-third of CRC predisposition. Most of hereditary CRC syndromes were diagnosed at the age of lower than 70, whereas little is known about the mutational profiles Chinese patients and their correlations with clinical features.
Method: In our present research, we retrospectively collected 731 patients who were diagnosed as CRC from Sun Yat-sen University Cancer Center, with ages lower than 70. All of them received genetic mutation detection consisting of a set of 14 specific inherited genes, which used target area capture and the second-generation high throughput sequencing technology. The characteristics of he patients with or without mutations were compared. We applied several comparison analysis to investigate the germline mutations distribution of genes that associated with the defined hereditary CRC syndromes in Chinese cohort.
Results: 397 patients (54.3%) harbored functionally variants of the 14 genes in CRC patients that diagnosis lower than 70. Intriguingly, we observed no statistical difference for clinical factors such as age, sex, smoke, drink, family history, pathology grade, clinic stage and overall survival between groups. In Mut group, the mutation frequency of each genes are MLH1(21.4%), MSH2(17.6%), MSH6(15.1%), PMS2(9.3%), EPCAM(8.3%), MLH3(8.1%), AXIN2(7.1%), PMS1(4.0%), MUTYH(12.8%), APC(12.3%), STK11(3.5%), BMPR1A(1.8%), SMAD4(0.3%), PTEN(1.0%). Genome mutual exclusivity analysis has identified a set of genes such as MLH1, MSH2, MUTYH, MSH6, APC and PMS2, for which most pairwise combinations are found rarely cooccurred. In correlation analysis between mutational genes and clinical features, pathology grade correlates strongly with PMS1 and SMAD4(P&lt;0.05). Tumor location correlates strongly with APC, MLH1, MSH2 and MSH6(P&lt;0.05). In mutation group, the ratio of Lynch syndrome and non-Lynch is 76.8% and 23.2%, respectively.
Conclusion: The clinic features of two groups have no statistic difference, which suggested other genes undiscovered may play a partial role in pathogenesis of patients of non-MUT group. In summary, we conducted a retrospective study to lead a comprehensive comparison of mutational profiles between MUT and non-MUT hereditary CRC patients, which supplemented the limited data of hereditary CRC in China.
Citation Format: Feng Wang, Qi Zhao, Teng-jia Jiang, Ying-nan Wang, Fu-rong Liu, Jia-jia Hu, Pei-rong Ding, Zhi-zhong Pan, Jian-yong Shao, Rui-hua Xu. Germline mutational profileof Chinese patients with colorectal cancer and diagnosed lower than 70 years [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 4161.