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BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Comparative analysis of copy number variations in ulcerative colitis associated and sporadic colorectal neoplasia

Authors: B. M. Shivakumar, Sanjiban Chakrabarty, Harish Rotti, Venu Seenappa, Lakshmi Rao, Vasudevan Geetha, B. V. Tantry, Hema Kini, Rajesh Dharamsi, C. Ganesh Pai, Kapaettu Satyamoorthy

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

The incidence of and mortality from colorectal cancers (CRC) can be reduced by early detection. Currently there is a lack of established markers to detect early neoplastic changes. We aimed to identify the copy number variations (CNVs) and the associated genes which could be potential markers for the detection of neoplasia in both ulcerative colitis-associated neoplasia (UC-CRN) and sporadic colorectal neoplasia (S-CRN).

Methods

We employed array comparative genome hybridization (aCGH) to identify CNVs in tissue samples of UC nonprogressor, progressor and sporadic CRC. Select genes within these CNV regions as a panel of markers were validated using quantitative real time PCR (qRT-PCR) method along with the microsatellite instability (MSI) in an independent cohort of samples. Immunohistochemistry (IHC) analysis was also performed.

Results

Integrated analysis showed 10 overlapping CNV regions between UC-Progressor and S-CRN, with the 8q and 12p regions showing greater overlap. The qRT-PCR based panel of MYC, MYCN, CCND1, CCND2, EGFR and FNDC3A was successful in detecting neoplasia with an overall accuracy of 54 % in S-CRN compared to that of 29 % in UC neoplastic samples. IHC study showed that p53 and CCND1 were significantly overexpressed with an increasing frequency from pre-neoplastic to neoplastic stages. EGFR and AMACR were expressed only in the neoplastic conditions.

Conclusion

CNVs that are common and unique to both UC-associated and sporadic colorectal neoplasm could be the key players driving carcinogenesis. Comparative analysis of CNVs provides testable driver aberrations but needs further evaluation in larger cohorts of samples. These markers may help in developing more effective neoplasia-detection strategies during screening and surveillance programs.
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Metadata
Title
Comparative analysis of copy number variations in ulcerative colitis associated and sporadic colorectal neoplasia
Authors
B. M. Shivakumar
Sanjiban Chakrabarty
Harish Rotti
Venu Seenappa
Lakshmi Rao
Vasudevan Geetha
B. V. Tantry
Hema Kini
Rajesh Dharamsi
C. Ganesh Pai
Kapaettu Satyamoorthy
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2303-4

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