Mutational Signature Similarities and Differences Between Appendiceal Adenocarcinoma and Colorectal Cancer

At the 2023 World Congress on Gastrointestinal Cancers, Michael White, MD, MSc, MD Anderson Cancer Center at The University of Texas, Houston, Texas, presented a study examining the genomic landscape of appendiceal adenocarcinoma.

Dr White noted data from this study "demonstrate high-risk associations with TP53 mutations, as well as lower-risk mutational profiles with GNAS mutations" and "showed a higher rate of mismatch repair deficiency pathway alterations in up to 21% of these appendiceal adenocarcinomas, which is similar to the rate seen in colon and rectal cancers."

Transcript:

Good morning. I'm Michael White. I'm an assistant professor in the Department of Colon and Rectal Surgery at MD Anderson Cancer Center. At the 2023 World Congress on GI Cancers, I'll be presenting  an abstract looking at the whole exome sequencing of 855 appendiceal adenocarcinomas, as well as matched colon and rectal adenocarcinomas that were sequenced through the Natera ctDNA assay, allowing us to describe the largest cohort of appendiceal adenocarcinomas to date.

Excitingly, in this analysis, we were able to demonstrate that appendiceal adenocarcinoma has a distinct mutational profile as compared to colon and rectal cancers, which has been well described previously. But more importantly, we're also able to demonstrate high-risk associations with TP53 mutations, as well as lower-risk mutational profiles with GNAS mutations. This has been demonstrated both in ctDNA positivity as well as the stage of disease.

We also were able to demonstrate that, while tumor mutational burden and microsatellite instability rates were low in appendiceal adenocarcinomas and significantly lower than matched colon and rectal tumors, that mismatch repair deficiency pathways through the COSMIC mutational signature showed a higher rate of mismatch repair deficiency pathway alterations in up to 21% of these appendiceal adenocarcinomas, which is similar to the rate seen in colon and rectal cancers.

So we're hopeful that current trials ongoing looking at immune checkpoint blockade and this rare malignancy may bear out further results in responsiveness to immunotherapy for appendiceal adenocarcinomas.

Source:

White M, Helmink B, Rivero-Hinojosa S, et al. The genomic landscape of appendiceal adenocarcinoma revealed by 855 whole exome sequences. Presented at World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract O-11