Abstract 4613: The difference of molecular signatures in left- and right-sided colorectal cancer Chinese patients
Authors: Zhang Sen , Guo Yun , Shu Weibin , Li Hui , Wang Yu , Zhao Wei , Wang Zusen , Yao Xueqing , Xiang Tao , Li Yong , Deng Ting , Ma Ruobing , Cui Qiang , Mei Lei , Lou Yang , Mu Shuo , Szallasi Zoltan , Zhang Yongchang , Yao Ming , Wang Kai 
Published: August 2018

Abstract
Background: Recent reports have demonstrated inferior outcomes for patients with right-sided colorectal cancer (RCC) compared to left-sided (LCC) as well as differences in treatment response based on disease sidedness. Molecular analyses provide a partly biologic explanation for the association with anatomic location, but molecular variations between RCC and LCC remain undefined in Chinese patients.
Methods: Tumors with origins clearly defined as cecum to transverse colon for RCC, and descending colon to rectum for LCC. The FFPE tumor and matched blood samples of 61 Chinese colorectal cancer patients including 39 males (64%) and 22 females (36%) with a mean age of 56 years old (yrs) were subjected to comprehensive genomic profiling (CGP) assay consisting of 450 gene full exons and selected introns in 39 genes. We measured the genomic alterations and calculated tumor mutational burden (TMB) of total somatic substitutions and insertions/deletions per megabase after filtering known driver mutations. Chi-square tests were used for comparative analyses.
Results: Among 61 primary samples, 44 were LCC with a median age of 55 yrs and 17 were RCC with a median age of 58 yrs. Genomic alterations of BRAF, ARID1A, TERT, high TMB values and MSI-High were significantly more prevalent in RCC. BRAF was mutated in 25% of RCC compared to 2.3% in LCC (p=0.006). ARID1A and TERT were mutated in 37.5% and 25% of RCC respectively but none in LCC (p&lt;0.05). The median TMB values were 18 vs. 7.2 muts/Mb for RCC vs. LCC (p&lt;0.01). No significant difference was found in PIK3CA (37.5.4% vs. 18.6%), ERBB2 (6.2% vs. 9.3%) and SMAD4 (25% vs. 16.3%). MSI-high tumors were more likely to occur in RCC rather than LCC (30.8% vs. 7.3%; p = 0.07). Moreover, there were more DNA repair-related genes and MMR genes mutations in RCC, including BRCA2 (25% vs. 4.7%), FANCL (12.5% vs. 0%), PTEN (37% vs. 4.7%), MSH6 (25% vs. 2.3%), and PALB2 (12.5% vs. 2.3%). For LCC, there were more mutations of KRAS (53.5% vs. 43.7%), APC (67.4% vs. 56.2%) and TP53 (74.4% vs. 62.5%), though these differences did not rise to the level of statistical significance.
Conclusions: The molecular difference between RCC and LCC is probably related to the finding that the mutations of DNA repair and MMR genes were more commonly detected in the right-sided colorectal cancer. Higher TMB values and MSI-high status could predict a higher response rate to immune checkpoint inhibitors to RCC patients instead of LCC. A better understanding of anatomic location and disease biology may help to identify therapeutic targets and precision medicine.
Citation Format: Sen Zhang, Yun Guo, Weibin Shu, Hui Li, Yu Wang, Wei Zhao, Zusen Wang, Xueqing Yao, Tao Xiang, Yong Li, Ting Deng, Ruobing Ma, Qiang Cui, Lei Mei, Yang Lou, Shuo Mu, Zoltan Szallasi, Yongchang Zhang, Ming Yao, Kai Wang. The difference of molecular signatures in left- and right-sided colorectal cancer Chinese patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4613.