Retrospective Analysis of Mutational Frequencies in Primary Versus Metastasis
Maryam J Zenali, Zesheng Liu, Gordon B Mills, Dawen Sui, Russell Broaddus, Stanley Hamilton. The University of Texas MD Anderson Cancer Center, Houston, TX
Background: Tumor biology, in regards to gene mutational status, can be affected by site (primary or metastasis). This phenomenon can potentially impact tumor sampling and therapeutic options. To evaluate mutational frequencies, and to determine whether the observed rate of mutations (KRAS, NRAS, BRAF, KIT, PIK3CA) are affected by site, we performed retrospective analysis of our patient's database, focusing on melanoma and colorectal adenocarcinomas.
Design: Molecular diagnostic lab data, in last 6 years, were collected in 1276 patients. Chart review was performed to evaluate diagnosis of specimen tested, tested genes and results, tumor site, and treatment options. Chi- squared or Fisher's exact tests were used to detect associations between site and the results (positive or negative) in each gene tested.
Results: Cases included 438 melanoma, 673 colorectal adenocarcinoma, 23 appendiceal adenocarcinoma, 17 small bowel adenocarcinoma, 33 pancreaticobiliary adenocarcinoma, and 17 neuroendocrine tumors and hepatocellular carcinoma, and 75 other types of adenocarcinoma, see figures 1-2 for analyzed results in melanoma and colorectal adenocarcinoma. Subset of cases showed co-mutations, majority in both PIK3CA and MEK pathways.
Conclusions: BRAF mutation was more seen in a metastatic site rather than primary in melanoma (p=0.023). In colorectal adenocarcinoma, NRAS mutation was more likely persent in metastatic site than primary (p=0.048). We did not find association with examined site in other analyzed mutations (KRAS, KIT, PIK3CA). These results suggest importance of consideration of disease site when analyzing mutational status. Probability of co-mutations in different pathways has significance for decisions regarding therapy.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 261, Wednesday Morning