MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques.

TitleMLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques.
Publication TypeJournal Article
Year of Publication2018
AuthorsBrammer, DW, Gillespie, PJ, Tian, M, Young, D, Raveendran, M, Williams, LE, Gagea, M, Benavides, FJ, Perez, CJ, Broaddus, RR, Bernacky, BJ, Barnhart, KF, Alauddin, MM, Bhutani, MS, Gibbs, RA, Sidman, RL, Pasqualini, R, Arap, W, Rogers, J, Abee, CR, Gelovani, JG
JournalProc Natl Acad Sci U S A
Date Published2018 Mar 13
KeywordsAnimals, Colorectal Neoplasms, Hereditary Nonpolyposis, Female, Macaca mulatta, Male, Microsatellite Instability, MutL Protein Homolog 1, Polymorphism, Single Nucleotide, Positron Emission Tomography Computed Tomography, Primate Diseases

Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques () at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon. These colon carcinoma lesions selectively accumulated [F]fluorodeoxyglucose ([F]FDG) and [F]fluoroacetate ([F]FACE) at high levels, reflecting elevated carbohydrate and fatty acid metabolism in these tumors. In contrast, the accumulation of [F]fluorothymidine ([F]FLT) was less significant, reflecting slow proliferative activity in these tumors. The diagnoses of colon carcinomas were confirmed by endoscopy. The expression of MLH1, MSH2, and MSH6 proteins and the degree of microsatellite instability (MSI) was assessed in colon carcinomas. The loss of MLH1 protein expression was observed in all tumors and was associated with a deletion mutation in the promoter region and/or multiple single-nucleotide polymorphism (SNP) mutations in the gene. All tumors exhibited various degrees of MSI. The pedigree analysis of this rhesus macaque population revealed several clusters of affected animals related to each other over several generations, suggesting an autosomal dominant transmission of susceptibility for colon cancer. The newly discovered hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques, termed -rheMac, may serve as a model for development of novel approaches to diagnosis and therapy of Lynch syndrome in humans.

Alternate JournalProc Natl Acad Sci U S A
PubMed ID29490919
PubMed Central IDPMC5856559

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