Fine deletion mapping of chromosome 2q21-37 shows three preferentially deleted regions in oral cancer

Abstract

We analysed the loss of heterozygosity (LOH) of long arm of chromosome 2 by using 16 polymorphic microsatellite markers in 39 matched oral normal and cancer tissues, and defined the deletional mapping of the region with putative tumor suppressor genes. LOH was detected at least one location in 33 of 39 (85%) tumor tissues. Frequent deletions were detected at the locations of microsatellite markers, D2S2304 (35%), D2S111 (40%), D2S155 (35%), D2S1327 (29%), D2S164 (29%), D2S125 (68%) and D2S140 (32%). Three preferentially deleted regions at 2q21-24, 2q33-35 and 2q37.3 were observed. Several candidate tumor suppressor genes in these regions such as LRP1B, CASP8, CASP10, BARD1, ILKAP, PPP1R7, and ING5, are located. Further molecular analysis of each gene should be performed to clarify their roles in oral carcinogenesis.

Inhibitor of Growth (ING) Family: An Emerging Molecular Target for Cancer Therapy

“…Similarly, we and other groups reported chromosomal deletion and/or decrease of ING4 expression in head and neck cancers 21) , glioma 62) and breast cancer 63) . Regarding with ING5, we detected allelic loss 64) , tumor-specific mutation and for growth inhibition 67) . Previous studies have likewise implicated …”

Array comparative genomic hybridization analysis of olfactory neuroblastoma

“…20q13.3, frequently overexpressed in ovarian cancers, has been recently shown to localize the BRK tyrosine kinase gene (GeneID: 5753), which is thought to have an important role in the development of ovarian cancers. 16 Losses occurring at chromosome 2q have been described for various carcinomas, including head and neck squamous cell carcinoma, [17][18][19] breast carcinoma, 20 lung carcinoma, 21 neuroblastoma, 22 cervical cancer, 23 and prostate adenocarcinoma. 24 Studies using different approaches have increasingly shown that the most affected region is 2q32-q37.…”

“…Three olfactory neuroblastomas were studied by Riazimand et al 5 using conventional CGH, and amplification of whole chromosome 19, partial gains of 1p, 8q, 15q, and 22q, and deletions of 4q and 6p were detected. Szymas et al 6 studied a single olfactory neuroblastoma and found gains of whole chromosomes 4,8,11, and 14, partial gains of 1q and 17q, partial deletions of 5q and 17q, and whole chromosome losses of 16,18,19, and X. In our study, we applied for the first time an oligonucleotide-based array CGH (aCGH) to identify the most frequently occurring DNA copy number changes in 13 cases of olfactory neuroblastoma.…”

Role of ING Family Genes in Head and Neck Cancer and Their Possible Applications in Cancer Diagnosis and Treatment

“…We demonstrated a high ratio of LOH in oral cancer using 16 microsatellite markers on the long arm of chromosome 2q21-37.3 [24]. ING5 appeared to be a strong candidate tumor suppressor in this study though several other candidate TSGs including ILKAP, HDAC4, PPP1R7, DTYMK, STK25, BOK are also localized at the area, where frequent deletion has been detected [11,12,24]. Moreover, our recent study revealed decreased expression of ING5 mRNA and mutations in oral cancer samples as compared to their corresponding normal controls, suggesting its tumor suppressive role in cancer [25].…”

“…Our continuous efforts led to identification of ING3 [14]. Following these works, other groups and our group published investigations on other members of ING family including ING2, ING4 and ING5 [15,16,[24][25][26][27][28][29][30][31][32]. Although almost all of the ING family members are known to be negative regulator of the cell growth, recent studies also demonstrated some of the members or splicing variants also functioning as oncogene, thus complicating the role of these genes in human carcinogenesis [31,32].…”