Mucinous Histology, BRCA1/2 Mutations, and Elevated Tumor Mutational Burden in Colorectal Cancer

Noa Harpaz; Yair Eli Gatt; Roy Zvi Granit; Hila Fruchtman; Ayala Hubert; Albert Grinshpun

doi:10.1155/2020/6421205

Mucinous Histology, BRCA1/2 Mutations, and Elevated Tumor Mutational Burden in Colorectal Cancer

J Oncol. 2020 Apr 25:2020:6421205. doi: 10.1155/2020/6421205. eCollection 2020.

Authors

Noa Harpaz¹, Yair Eli Gatt², Roy Zvi Granit¹, Hila Fruchtman³, Ayala Hubert¹, Albert Grinshpun¹

Affiliations

¹ Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
² Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
³ Radiology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Abstract

Mucinous colorectal carcinomas (MC) constitute 10% of colorectal malignancies. Recently, an increased risk of colorectal cancer has been demonstrated in germline BRCA1/2 mutation carriers. Furthermore, BRCA1/2 germline mutation carriers have exhibited a higher-than-expected frequency of MC tumors. Here, we investigate the relationship between BRCA mutations and mucinous histology in colorectal carcinoma patients, using both an existing cohort of sequenced colorectal tumors and a prospective case-control study comparing MC and conventional adenocarcinoma (AC) patients tested for BRCA mutations. We discovered that MC tumors exhibit a statistically significantly higher incidence of BRCA mutations in addition to a higher average mutation count when compared to AC tumors in the existing cohort. The strongest predictor of the mutation count was mucinous histology, independently of other variables including microsatellite instability. Contrary to our hypothesis, the first association did not recur in the prospective case-control study, likely due to our pathological definition of MC tumors and small sample size. Finally, we observed a higher tumor mutational burden (TMB) in MC tumors compared with AC tumors. We suggest that the association between MC histology, BRCA mutations, and increased TMB may open the door to the utilization of simple tests (such as histopathologic characterization) to detect patients who may benefit from immunotherapy in colorectal cancer.