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Mol Cancer Res. 2014 Jun;12(6):823-9. doi: 10.1158/1541-7786.MCR-13-0624. Epub 2014 Mar 20.

HD chromoendoscopy coupled with DNA mass spectrometry profiling identifies somatic mutations in microdissected human proximal aberrant crypt foci.

Author information

1
Authors' Affiliations: Center for Molecular Medicine; Colon Cancer Prevention Program, Neag Comprehensive Cancer Center, School of Medicine, University of Connecticut Health Center, Farmington, Connecticut; and.
2
Division of Gastroenterology; Colon Cancer Prevention Program, Neag Comprehensive Cancer Center, School of Medicine, University of Connecticut Health Center, Farmington, Connecticut; and.
3
Department of Pathology and Laboratory Medicine, Boston Medical Center, Boston, Massachusetts.
4
Authors' Affiliations: Center for Molecular Medicine; Colon Cancer Prevention Program, Neag Comprehensive Cancer Center, School of Medicine, University of Connecticut Health Center, Farmington, Connecticut; and rosenberg@uchc.edu.

Abstract

Despite increased implementation of screening colonoscopy, interval cancers in the proximal colon remain a major public health concern. This fact underscores the limitations of current screening paradigms and the need for developing advanced endoscopic techniques. The density of aberrant crypt foci (ACF), the earliest identifiable mucosal abnormality, may serve as a surrogate marker for colon cancer risk, but has rarely been studied in the proximal colon. To this end, high-definition (HD) chromoendoscopy was conducted to define the relevance of ACF in the proximal colon. In addition, due to limited ACF size, the development of a combinatorial approach was required to maximize data acquisition obtained from individual biopsy samples. Proximal and distal ACF samples were characterized for a total of 105 mutations across 22 known tumor suppressor and proto-oncogenes using high-throughput Sequenom MassARRAY analysis. From this profiling, a discrete number of somatic mutations were identified, including APC(R876*) and FLT3(I836M), as well as a deletion within the EGFR gene. Combined, these data highlight the significance of ACF within the context of colon cancer pathogenesis, particularly in the proximal colon.

IMPLICATIONS:

The identification of cancer-related mutations in commonly overlooked mucosal lesions underscores the preventive benefit of implementing advanced endoscopic screening to larger patient populations, particularly in the proximal colon. Visual Overview: http://mcr.aacrjournals.org/content/early/2014/05/22/1541-7786.MCR-13-0624/F1.large.jpg. Mol Cancer Res; 12(6); 823-9. ©2014 AACR.

PMID:
24651453
PMCID:
PMC4058342
DOI:
10.1158/1541-7786.MCR-13-0624
[Indexed for MEDLINE]
Free PMC Article

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