☆ 4.6 Article

Comparative molecular genomic analyses of a spontaneous rhesus macaque model of mismatch repair-deficient colorectal cancer

PLOS GENETICS (2022)

Journal

PLOS GENETICS

Volume 18, Issue 4, Pages -

Publisher

PUBLIC LIBRARY SCIENCE

DOI: 10.1371/journal.pgen.1010163

Keywords

Funding

Feinberg Family Foundation
MDACC Institutional Research Grant (IRG) Program
Cattlemen for Cancer Research [R24 OD011173, CA016672]

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Abstract

The study focused on Lynch Syndrome (LS), a genetic condition that increases the risk of developing colorectal cancer, and analyzed a non-human primate (NHP) model for studying hereditary colorectal cancer. By comparing different types of CRC in humans with tumors developed in monkeys, the study aimed to determine the accuracy of using this NHP model for studying early cancer development, treatment options, and prevention approaches in both hereditary and sporadic colorectal cancer.

Author summaryCRC remains the third most common cancer diagnosed in the United States. Some CRC may arise spontaneously without any known risk factors, while others may arise in patients with strong family history associated to inherited genetic syndromes. Our study focused on a genetic condition known as LS, which significantly increases the risk of developing CRC as well as several different types of cancers. Biological tools and laboratory animal models available for studying hereditary CRC remain limited and not always directly translatable to human disease. Therefore, our study presents a comprehensive analysis of a spontaneous non-human primate (NHP) model used to study the genetic contribution in Lynch Syndrome colorectal cancer. We performed a cross-comparison of different types of CRC in humans with tumors developed in monkeys to determine the accuracy of using this NHP model for studying early cancer development, treatment options, and prevention approaches in both hereditary and sporadic colorectal cancer displaying MMR deficiency. Colorectal cancer (CRC) remains the third most common cancer in the US with 15% of cases displaying Microsatellite Instability (MSI) secondary to Lynch Syndrome (LS) or somatic hypermethylation of the MLH1 promoter. A cohort of rhesus macaques from our institution developed spontaneous mismatch repair deficient (MMRd) CRC with a notable fraction harboring a pathogenic germline mutation in MLH1 (c.1029C

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Spontaneous regression of mismatch repair-deficient colorectal cancers: Case series

Takahiro Utsumi, Shin'ichi Miyamoto, Takahiro Shimizu, Kasumi Yokogawa, Yuki Nakanishi, Mitsuhiro Nikaido, Ayako Hirata, Miyu Nishida, Ikuo Aoyama, Tomoko Okuno, Akihiko Yoshizawa, Akihiro Kaneda, Yoshiharu Sakai, Chiharu Kawanami, Hiroshi Seno

Summary: Spontaneous regression in colorectal cancer is rare and often associated with specific endoscopic characteristics, lack of DNA mismatch repair proteins, and a deficiency in mismatch repair (dMMR). The activation of anti-tumor host immune responses through increased tumor-infiltrating lymphocytes may play a role in the spontaneous regression of colorectal cancer.

DIGESTIVE ENDOSCOPY (2021)