Assessing Novel Mutations in Colorectal Carcinoma Using Next-Generation Sequencing

Authors

• Craig Cousineau, Beaumont Health Resident
• Wei Li, Beaumont Health
• Jason Douglas, Beaumont Health Resident
• Harry Wasvary, Beaumont Health
• Bryan Thibodeau, Beaumont Health
• Claire Peeples, Beaumont Health

Document Type

Conference Proceeding

Publication Date

9-2018

Publication Title

Archives of Pathology and Laboratory Medicine

Abstract

Context: In the United States there are more than 130 000 new cases of colorectal cancer annually. Characterizing mutations involved in the pathogenesis of colorectal adenocarcinoma is an important step toward developing gene-based therapies. Next-generation sequencing (NGS) enables screening for variants in large panels of genes in tissues.

Design: We collected formalin-fixed, paraffin-embedded tissue from rectal adenocarcinoma cases, including biopsy and surgical resection specimens. Patients came from 2 groups: those with a complete response (CR) to preoperative therapy (n = 8), and those who responded poorly (NR, n = 8). NGS using the Human Comprehensive Cancer GeneRead DNAseq Targeted Panel, which screens for variants in 160 genes, was performed.

Results: In both groups we found mutations in genes previously implicated in colorectal cancer, including PTEN and NF1. Mutations in genes that have not been described in colorectal cancer, such as GNAQ (3 of 8 CR and 5 of 8 NR) and ATM (5 of 8 CR and 5 of 8 NR), were also identified.

Conclusions: GNAQ codes for a guanine nucleotide-binding protein that couples transmembrane receptors to intracellular pathways. Mutations have been reported in melanoma and ocular neoplasms. ATM is involved in cell division and repairing damaged DNA. ATM mutations have been described in several cancers, including breast and pancreatic. GNAQ and ATM mutations are novel findings in rectal carcinoma, present in 50% and 62.5% of specimens, respectively. Interestingly, all patients with the GNAQ mutation harbored the same variant. Going forward, we will confirm these mutations in additional specimens, and compare the mutation profile between NR and CR to identify mutations that predict response to therapy.

Volume

142

Issue

9

First Page

e4

Comments

College of American Pathologists Annual Meeting, October 20-24, 2018, Chicago, IL

Last Page

e5

Recommended Citation

Cousineau C, Li W, Douglas J, Wasvary H, Thibodeau B, Peeples C. Assessing novel mutations in colorectal carcinoma using next-generation sequencing. Arch Pathol Lab Med. 2018 Sep;142(9):e4-e5. doi:10.5858/arpa.2018-0293-AB

DOI

10.5858/arpa.2018-0293-AB