Novel tumor suppressor candidates on chromosome 3 revealed by NotI-microarrays in cervical cancer

• DOI: 10.4161/epi.24233
• Publication Date: 2013-03-29T21:32:58Z
• Authors: Vera N. Senchenko; Natalia P. Kissel...; Tatyana A. Ivanova; Alexey A. Dmitriev; George S. Krasnov; Anna V. Kudryavtseva; Grigory V. Panasenko; Evgeny B. Tsitrin; Michael I. Lerman; Fyodor L. Kisseljov; Vladimir I. Kashuba; Eugene R. Zabarovsky
• Keywords: Bisulfite sequencing; Bisulfite

Genetic and epigenetic alterations in cervical carcinomas were investigated using NotI-microarrays containing 180 cloned sequences flanking all NotI-sites associated with genes on chromosome 3. In total, 48 paired normal/tumor DNA samples, specifically enriched NotI-sites, hybridized to NotI-microarrays. Thirty genes, including tumor suppressors or candidates (for example, VHL, RBSP3/CTDSPL, ITGA9, LRRC3B, ALDH1L1, EPHB1) previously unknown as cancer-associated (ABHD5, C3orf77, PRL32, LOC285375, FGD5 others), showed methylation/deletion 21–44% of tumors. The more frequently altered squamous cell (SCC) than adenocarcinomas (ADC, p < 0.01). A set seven potential markers (LRRN1, PRICKLE2, BHLHE40, RBSP3, CGGBP1 SOX14) is promising for discrimination ADC SCC. Alterations 20 simultaneously revealed 23% Bisulfite sequencing analysis confirmed methylation a frequent event High down-regulation frequency was shown VILL, APRG1/C3orf35 RASSF1 (isoform A) (3p21.3 locus) Both extent RASSF1A RBSP3 mRNA level decrease pronounced tumors lymph node metastases compared non-metastatic ones (p ≤ 0.05). We by bisulfite that promoter rare SCC and, the first time, demonstrated at both protein levels without this histological type. Thus, our data novel suppressor located 3 loss stability 3p21.3 locus combination cancer.