Use of NotI microarrays in analysis of epigenetic and structural changes in epithelial tumor genomes by the example of human chromosome 3

Integrin alpha9 (ITGA9) expression and epigenetic silencing in human breast tumors

“…30 From the other side, frequent genetic/epigenetic aberrations (deletions, methylation) of ITGA9 were identified in different epithelial cancers using NotI-microarray. [33][34][35][36] Taken together, the presented data suppose an existence of different molecular pathways participating in the regulation of ITGA9 expression in cancer and resulting in the heterogeneity of primary tumors based on ITGA9 expression level. In fact, it was shown for different cell lines in vitro that colon adenocarcinoma Caco-2 and T84 cells express the integrin alpha9 subunit while the five other colon carcinoma cell lines tested were negative for its expression, 31 two glioblastoma cell lines, LN229 and LN18 are alpha9beta1 integrin positive and negative, respectively.…”

“…If the first group seems to consist of the tumors with genetically eliminated ITGA9 (deletions, mutations), the second group of tumors should have a functional ITGA9 gene and some epigenetic mechanisms are possibly involved in the attenuation of ITGA9 expression in the cells. Earlier, ITGA9 CpG-island methylation was indeed shown in more than 30% of cervical 33 and colorectal 34 tumors. According to our data, hypermethylation of ITGA9 CpG-island could be an important mechanism for ITGA9 epigenetic inactivation in breast cancer responsible for its decreased expression in about 25% of primary breast tumors.…”

“…31 According to another study, ITGA9 has significantly higher expression levels in colorectal tumors with high microsatellite instability ( mechanisms of ITGA9 activation in cancer cells remain unclear; however the effect may unfavorably contribute to the cancer prognosis supporting ITGA9 as a potential target for anti-integrin therapy. From the other side, extensive search of genetic/epigenetic aberrations of ITGA9 by NotI-micorarray identified frequent (more than in 30%) aberrations (deletions, methylation) in kidney, lung, breast, ovary, cervical, prostate and colorectal cancer, 33,34 in 45-55% of head and neck squamous cell carcinomas 35 and 65% of uterine cervical carcinomas (41% deletion and 24% methylation). 36 A possibility of ITGA9 CpG-island methylation was verified in cervical 33 and colorectal 34 tumors by methylspecific PCR and bisulfite sequencing.…”

“…From the other side, extensive search of genetic/epigenetic aberrations of ITGA9 by NotI-micorarray identified frequent (more than in 30%) aberrations (deletions, methylation) in kidney, lung, breast, ovary, cervical, prostate and colorectal cancer, 33,34 in 45-55% of head and neck squamous cell carcinomas 35 and 65% of uterine cervical carcinomas (41% deletion and 24% methylation). 36 A possibility of ITGA9 CpG-island methylation was verified in cervical 33 and colorectal 34 tumors by methylspecific PCR and bisulfite sequencing.…”

Von Hippel-Lindau gene expression in human endometrium during menstrual cycle

“…It is widely expressed in a variety of tissues, demonstrating that the expression of the VHL gene transcript is not restricted to organs affected by the VHL disease (5). Mutations of the VHL gene were associated with carcinogenesis in various organs, including the kidney, lung, breast, eye, ovary and cervix (6). Additionally, a deficiency or inactivation of the VHL gene is able to cause ovarian tumors and uterine cervix carcinoma (7,8).…”