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. 2016 May 28;22(20):4936-45.
doi: 10.3748/wjg.v22.i20.4936.

Longitudinal molecular characterization of endoscopic specimens from colorectal lesions

Petra Minarikova  1 , Lucie Benesova  1 , Tereza Halkova  1 , Barbora Belsanova  1 , Stepan Suchanek  1 , Jiri Cyrany  1 , Inna Tuckova  1 , Jan Bures  1 , Miroslav Zavoral  1 , Marek Minarik  1
Affiliations

Longitudinal molecular characterization of endoscopic specimens from colorectal lesions

Petra Minarikova et al. World J Gastroenterol. .

Abstract

Aim: To compare molecular profiles of proximal colon, distal colon and rectum in large adenomas, early and late carcinomas. To assess feasibility of testing directed at molecular markers from this study in routine clinical practice.

Methods: A prospective 3-year study has resulted in the acquisition of samples from 159 large adenomas and 138 carcinomas along with associated clinical parameters including localization, grade and histological type for adenomas and localization and stage for carcinomas. A complex molecular phenotyping has been performed using multiplex ligation-dependent probe amplification technique for the evaluation of CpG-island methylator phenotype (CIMP), PCR fragment analysis for detection of microsatellite instability and denaturing capillary electrophoresis for sensitive detection of somatic mutations in KRAS, BRAF, TP53 and APC genes.

Results: Molecular types according to previously introduced Jass classification have been evaluated for large adenomas and early and late carcinomas. An increase in CIMP+ type, eventually accompanied with KRAS mutations, was notable between large adenomas and early carcinomas. As expected, the longitudinal observations revealed a correlation of the CIMP+/BRAF+ type with proximal location.

Conclusion: Prospective molecular classification of tissue specimens is feasible in routine endoscopy practice. Increased frequency of some molecular types corresponds to the developmental stages of colorectal tumors. As expected, a clear distinction is notable for tumors located in proximal colon supposedly arising from the serrated (methylation) pathway.

Keywords: BRAF; Colorectal cancer; CpG-island methylator phenotype; DNA; Microsatellite instability.

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Figures

Figure 1
Figure 1
Longitudinal frequency of CpG-island methylator phenotype phenotype in different tumor types. CIMP: CpG-island methylator phenotype.
Figure 2
Figure 2
Molecular classification of colorectal carcinomas (all stages) using classification according to Jass and others[30-32]. MSI: Microsatellite instability; CIN: Chromosomal instability; CIMP: CpG-island methylator phenotype.
Figure 3
Figure 3
Evaluation workflows for assignment of Jass types in large adenomas (A), early carcinomas (B) and late carcinomas (C).
See this image and copyright information in PMC

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References

    1. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med. 2009;361:2449–2460. - PMC - PubMed
    1. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988;319:525–532. - PubMed
    1. Konishi M, Kikuchi-Yanoshita R, Tanaka K, Muraoka M, Onda A, Okumura Y, Kishi N, Iwama T, Mori T, Koike M, et al. Molecular nature of colon tumors in hereditary nonpolyposis colon cancer, familial polyposis, and sporadic colon cancer. Gastroenterology. 1996;111:307–317. - PubMed
    1. Jass JR. Towards a molecular classification of colorectal cancer. Int J Colorectal Dis. 1999;14:194–200. - PubMed
    1. Kim JC, Cho YK, Roh SA, Yu CS, Gong G, Jang SJ, Kim SY, Kim YS. Individual tumorigenesis pathways of sporadic colorectal adenocarcinomas are associated with the biological behavior of tumors. Cancer Sci. 2008;99:1348–1354. - PMC - PubMed

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