Study of Potential Mutations in the Genetic Profiles of Rectal Cancer Patients Before and After Neoadjuvant Chemoradiation

Document Type

Conference Proceeding

Publication Date

9-2020

Publication Title

Archives of Pathology and Laboratory Medicine

Abstract

Context: Less than 50% of locally advanced rectal cancer respond to presurgical neoadjuvant chemoradiation (nCRT). Identifying a method to predict response of rectal tumors to nCRT prior to surgery would help to select appropriate treatment options for rectal cancer patients. We aimed to study potential mutations in genetic profiles of rectal cancer patients before and after nCRT using next-generation sequencing. Design: Biopsy and surgical resection specimens from rectal adenocarcinoma cases were collected and divided into 2 groups: those with a complete response to preoperative therapy (n¼9) and those who responded poorly (n ¼ 9). Next-generation sequencing using the Human Comprehensive Cancer GeneRead DNAseq Targeted Panel, which screens for variants in 160 genes, was performed. Results: We identified 195 variants in 83 genes in tissue specimens, including mutations in PTEN, ATM, APC, GNAQ, FGFR3, TP53, PIK3CA, BRCA2, EP300, and MSH6. The number of identical variants were found in multiple patients. These genes are all implicated in colorectal cancer biopathways. Poor responders showed mutations in 4 genes not mutated in complete responders: KDM6A, ABL1, DAXXZBTB22, and KRAS. Ten genes were mutated only in the complete responders, including ARID1A, PMS2, JAK1, CREBBP, MTOR, RB1, PRKAR1A, FBXW7, ATM C11orf65, and KMT2D, with specific discriminating variants noted in DMNT3A, KDM6A, MTOR, APC, and TP53. Conclusions: Our results show reduction in variant heterogeneity with treatment in both groups that was not statistically significant. We identified multiple genetic variations in tumor DNA from rectal cancer patients who are poor responders to neoadjuvant chemoradiation, compared to complete responders. Further investigation is warranted.

Volume

144

Issue

9S1

First Page

e183

Comments

College of American Pathologists Annual Meeting, October 10-14, 2020, Virtual

Last Page

e183

DOI

10.5858/arpa.2020-0991-AB

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