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

Abstract

BackgroundThe 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).MethodsWe 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.ResultsIntegrated 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.ConclusionCNVs 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2303-4) contains supplementary material, which is available to authorized users.

Bevacizumab and CCR2 Inhibitor Nanoparticles Induce Cytotoxicity-Mediated Apoptosis in Doxorubicin-Treated Hepatic and Non-Small Lung Cancer Cells

“…There is an increasing evidence to the vital antiproliferative effects of bevacizumab (avastin; AV) (Ferrara et al, 2005) and CCR2 antagonist (CR) (Monti et al, 2003;Wolf et al, 2012;Zhang et al, 2013;Zhang et al, 2010) , and recently their PLGA-based (Hao et al, 2009;Pan et al, 2011) and micelles-based (Roblek et al, 2015) nanoparticulates (NPs) on different cancer cells. One of the primary cancer types is hepatic cancer (HCC) (Goldstraw et al, 2011;Yang, 2009) and non-small cell lung cancer (NSCLC) is one of the most organs affected by metastasis (Shivakumar et al, 2016;Sasaki et al, 2011) .…”

“…Although the presence of different chemotherapeutic approaches for tackling HCC and NSCLC, drug resistance is still a remaining obstacle that finally ends up with cancer relapse. Hence, some missing acquaintances are present between the fundamental carcinogenic machineries and the current plans of drug development (Lynch et al, 2004;Shivakumar et al, 2016;Sasaki et al, 2011;Soucek et al, 2008;Rosell and Felip, 2001;Wu et al, 2011). Therefore, there is an urgent need for new therapeutic approaches for HCC and NSCLC.…”

Inflammatory bowel disease in India - Past, present and future

“…The same group also reports increasing number of copy number variations spanning multiple chromosomes to be associated with the progression of UC to CRC from low risk through high risk cases, dysplasia cases to CRC[ 96 ] some of which are common and unique to both UC associated and sporadic CRC. These are present in 10 overlapping regions of a number of chromosomes (highest in 12p and 8q chromosome) and have overall accuracy of 29% and 54% for detecting these cancers respectively[ 97 ].…”

Comprehensive molecular analysis based on somatic copy number alterations in intramucosal colorectal neoplasias and early invasive colorectal cancers

“…The incidence and mortality rate of CRC can be reduced by early detection and removal of treatable neoplasia; however, there is a lack of useful markers specific for both established invasive cancer and precancerous lesions [ 13 ]. Molecular stratification, combined with other alterations that are related to tumor evolution, may be suitable for evaluation of early colorectal carcinogenesis [ 13 ].…”