Frequent amplification of 8q24, 11q, 17q, and 20q‐specific genes in pancreatic cancer

Abstract

Genetic changes involved in the development and progression of pancreatic cancer are still partly unknown, despite the progress in recent years. In this study, comparative genomic hybridization analysis in 31 pancreatic cancer cell lines showed that chromosome arms 8q, 11q, 17q, and 20q are frequently gained in this tumor type. Copy number analysis of selected genes from these chromosome arms by fluorescence in situ hybridization showed amplification of the MYC oncogene in 54% of the cell lines, whereas CCND1 was amplified in 28%. In the 17q arm, the ERBB2 oncogene was amplified in 20% of the cell lines, TBX2 in 50%, and BIRC5 in 58%, indicating increased involvement toward the q telomere of chromosome 17. In the 20q arm, the amplification frequencies varied from 32% to 83%, with the CTSZ gene at 20q13 being most frequently affected. These results illustrate that amplification of genes from the 8q, 11q, 17q, and 20q chromosome arms is common in pancreatic cancer.

Characterization of gene expression in mucinous cystic neoplasms of the pancreas using oligonucleotide microarrays

“…Stk6 is located on an amplicon frequently amplified and overexpressed in breast (Hodgson et al, 2003), pancreatic (Mahlamaki et al, 2002;Li et al, 2003) and other cancers. A polymorphism in STK6 identified as a modifier of cancer risk in mice led to investigations demonstrating that the same 91A variant was associated with an increased risk of developing colon cancer and tumors were much more likely to amplify the 91A variant than the normal allele (Ewart-Toland et al, 2003).…”

Genetic alterations in 102 primary gastric cancers by comparative genomic hybridization: gain of 20q and loss of 18q are associated with tumor progression

“…Previous CGH studies of gastric cancers yielded similar results. Moreover, several CGH studies identified the 20q region as the most frequent site of gain of DNA in gastric [29][30][31][32]34,35,39 Amplification at 20q has been reported in several cancers, such as colon cancer, 40 pancreatic cancer, 41,42 lung adenocarcinoma, 43 ovarian carcinoma, 44 and osteosarcoma. 45 In our study, gain of 20q was detected in 71 cases (70%) and was associated with the pattern of the cancer-stroma 51 and CYP24 (20q13.2).…”

“…A gain in DNA copy number at 8q was the second most frequent gain, but it was not associated with clinicopathologic factors in our series. Amplification at 8q has been reported in several cancers, such as pancreatic cancer, 42 osteosarcoma, 45 and colorectal cancer. 40 The genes at 8q (8q-23-24) include the c-myc, EIF3S3 and PRL-3 genes.…”

Ectopic Tbx2 expression results in polyploidy and cisplatin resistance

“…Furthermore, both Tbx2 and Tbx3 are expressed in the developing breast (Jerome-Majewska et al, 2005) and their genes are amplified and/or overexpressed in some breast tumors (Sinclair et al, 2002;Packham and Brook, 2003) and in certain breast cancer cell lines Fan et al, 2004). Tbx2 is also overexpressed in 50% of pancreatic cancer cell lines (Mahlamaki et al, 2002) and in melanomas where it was shown to function as an anti-senescence factor (Vance et al, 2005). These results suggest that T-box factors may contribute to oncogenesis through suppressing senescence but whether additional mechanisms are involved remains to be elucidated.…”