Colorectal premalignancy is associated with consensus molecular subtypes 1 and 2.

Autor:	Chang K; Department of Clinical Cancer Prevention, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, USA; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, USA., Willis JA; Hematology and Oncology Fellowship Program, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA., Reumers J; Janssen Oncology Research & Development, Pharmaceutical Companies of Johnson & Johnson, Beerse, Belgium., Taggart MW; Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA., San Lucas FA; Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, USA., Thirumurthi S; Department of Gastroenterology Hepatology and Nutrition, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, USA., Kanth P; Division of Gastroenterology, University of Utah Huntsman Cancer Institute, Salt Lake City, USA., Delker DA; Division of Gastroenterology, University of Utah Huntsman Cancer Institute, Salt Lake City, USA., Hagedorn CH; Central Arkansas Veterans Healthcare System and University of Arkansas for Medical Sciences, Little Rock, USA., Lynch PM; Department of Gastroenterology Hepatology and Nutrition, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, USA., Ellis LM; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, USA., Hawk ET; Department of Clinical Cancer Prevention, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, USA., Scheet PA; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, USA., Kopetz S; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of GI Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA., Arts J; Janssen Oncology Research & Development, Pharmaceutical Companies of Johnson & Johnson, Beerse, Belgium., Guinney J; Sage Bionetworks, Fred Hutchinson Cancer Research Center, Seattle, USA., Dienstmann R; Sage Bionetworks, Fred Hutchinson Cancer Research Center, Seattle, USA; Oncology Data Science (ODysSey) Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Electronic address: rdienstmann@vhio.net., Vilar E; Department of Clinical Cancer Prevention, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, USA; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, USA; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of GI Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: evilar@mdanderson.org.
Jazyk:	angličtina
Zdroj:	Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2018 Oct 01; Vol. 29 (10), pp. 2061-2067.
DOI:	10.1093/annonc/mdy337
Abstrakt:	Background: Gene expression-based profiling of colorectal cancer (CRC) can be used to identify four molecularly homogeneous consensus molecular subtype (CMS) groups with unique biologic features. However, its applicability to colorectal premalignant lesions remains unknown. Patients and Methods: We assembled the largest transcriptomic premalignancy dataset by integrating different public and proprietary cohorts of adenomatous and serrated polyps from sporadic (N = 311) and hereditary (N = 78) patient populations and carried out a comprehensive analysis of carcinogenesis pathways using the CMS random forest (RF) classifier. Results: Overall, transcriptomic subtyping of sporadic and hereditary polyps revealed CMS2 and CMS1 subgroups as the predominant molecular subtypes in premalignancy. Pathway enrichment analysis showed that adenomatous polyps from sporadic or hereditary cases (including Lynch syndrome) displayed a CMS2-like phenotype with WNT and MYC activation, whereas hyperplastic and serrated polyps with CMS1-like phenotype harbored prominent immune activation. Rare adenomas with CMS4-like phenotype showed significant enrichment for stromal signatures along with transforming growth factor-β activation. There was a strong association of CMS1-like polyps with serrated pathology, right-sided anatomic location and BRAF mutations. Conclusions: Based on our observations made in premalignancy, we propose a model of pathway activation associated with CMS classification in colorectal carcinogenesis. Specifically, while adenomatous polyps are largely CMS2, most hyperplastic and serrated polyps are CMS1 and may transition into other CMS groups during evolution into carcinomas. Our findings shed light on the transcriptional landscape of premalignant colonic polyps and may help guide the development of future biomarkers or preventive treatments for CRC.
Databáze:	MEDLINE
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