Small-bowel adenocarcinoma shows unique genomic profile

Last Updated: 2017-06-21

By David Douglas

NEW YORK (Reuters Health) - Genomic profiling demonstrates that small-bowel adenocarcinoma (SBA) is significantly different from colorectal cancer and gastric carcinoma, according to a large study.

As Michael J. Overman told Reuters Health by email, "The unique genomic alterations seen in small-bowel adenocarcinoma in comparison to gastric and colon establish this cancer as a unique intestinal cancer and specific research efforts tailored to this rare cancer are needed."

In a paper online June 15 in JAMA Oncology, Dr. Overman of the University of Texas MD Anderson Cancer Center in Houston, and colleagues note that SBA is often "not diagnosed preoperatively; instead, it is found incidentally during surgical exploration for a small-bowel obstruction. Thus, there is a great need for a robust genomic analysis."

To help fill that need, the team prospectively analyzed tissue samples from more than 7,000 patients. These included 317 with SBA, 6353 with colorectal cancer and 889 with gastric carcinoma. Testing involved a large genomic platform covering 236 of 315 cancer-related genes and selected rearrangements.

The profiling was undertaken in the course of clinical care at the request of the treating physicians in order to aid therapy decisions.

The frequency of adenomatous polyposis coli (APC) alterations was significantly lower in SBA (26.8%) than in colorectal cancer (75.9%) but significantly higher than in gastric carcinoma (7.8%).

Other commonly altered genes (involving more than 10% of cases) included were TP53, KRAS, SMAD4, PIK3CA, CDKN2A, and ARID1A.

For example, the frequency of CDKN2A alterations was 14.5% in SBA and 2.6% in colorectal cancer. For KRAS alterations, it was 53.6% in SBA and 14.2% in gastric carcinoma.

In addition, ERBB2/HER2 point mutations, microsatellite instability (MSI) and high tumor mutational burden (TMB) were all enriched in SBA.

Furthermore, say the researchers, "Significant differences were noted in the molecular profile of unspecified SBA compared with duodenal adenocarcinoma, as well as in inflammatory bowel disease-associated SBAs."

The findings, they point out, "stress the need for further biological understanding of this rare cancer. In addition, this effort has uncovered a number of unique targetable alterations and a higher rate of MSI and increased TMB in SBA, representing direct clinical relevance."

In particular, concluded Dr. Overman, "The high rate of MSI-high within small-bowel adenocarcinoma demonstrate the need for testing all small-bowel adenocarcinoma patients for MSI, in order to enable the use of the FDA approved anti-pd1 agent pembrolizumab which is approved for solid cancers that are MSI-high."

SOURCE: http://bit.ly/2rUR80q

JAMA Oncol 2017.