Genetic editing of colonic organoids provides a molecularly distinct and orthotopic preclinical model of serrated carcinogenesis
Abstract
Serrated colorectal cancer (CRC) accounts for approximately 25% of cases and includes tumours that are among the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen-activated kinase pathway gene, BRAF, and epigenetic modifications termed the CpG Island Methylator Phenotype, leading to epigenetic silencing of key tumour suppressor genes. It is still not clear which (epi-)genetic changes are most important in neoplastic progression and we begin to address this knowledge gap herein.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 17, 2018
- Source ID
- 10.1136/gutjnl-2017-315920
Entities
People
- Barbara A Leggett
- Daniel L Worthley
- Helen E Abud
- Hiroki Kobayashi
- Jatin Roper
- Jia Q Ng
- Josephine A Wright
- Julie Marker
- Krystyna Gieniec
- Laura Vrbanac
- Lisa Jonavicius
- Lochlan Fennell
- Mari Ichinose
- Mark L Bettington
- Miao Yang
- Nobumi Suzuki
- Pratyaksha Wirapati
- Roshini Somashekar
- Sabine Tejpar
- Siddhartha Mukherjee
- Simon J Leedham
- Sonja Klebe
- Susan Woods
- Tamsin R M Lannagan
- Tongtong Wang
- Tracey L Putoczki
- Vicki L J Whitehall
- Yoku Hayakawa
- Young K Lee
- Ömer H. Yılmaz
Organizations
- American Federation for Aging Research
- Gastroenterological Society of Australia
- Koch Institute for Integrative Cancer Research at MIT
- National Cancer Institute
- National Health and Medical Research Council
- National Institutes of Health
- Sidney Kimmel Foundation
- United States Department of Defense
- V Foundation for Cancer Research