We have previously shown that the gap junction protein γ 1 (GJC1) gene, encoding the connexin-45 protein, is inactivated by promoter hypermethylation in colorectal cancer. This was confirmed in a recent Endocrine-Related Cancer publication analyzing a limited number of samples. The aim of this study was to analyze GJC1 in a larger clinical cohort (n=485) and to assess whether or not the promoter hypermethylation was associated with clinical or pathological features. The methylation of GJC1 was confirmed to be tumor specific and was observed in 33% of colorectal cancers and 12% of adenomas. The methylation was strongly associated with BRAF mutations (P=5.64×10−13) as well as with proximal tumor location (P=1.42×10−3), features compatible with a CpG island methylator phenotype.
Deeqa Ahmed, Ragnhild A Lothe, Edgar Rivedal, and Guro E Lind
Andreas M Hoff, Sigrid M Kraggerud, Sharmini Alagaratnam, Kaja C G Berg, Bjarne Johannessen, Maren Høland, Gro Nilsen, Ole C Lingjærde, Peter W Andrews, Ragnhild A Lothe, and Rolf I Skotheim
Testicular germ cell tumours (TGCTs) appear as different histological subtypes or mixtures of these. They show similar, multiple DNA copy number changes, where gain of 12p is pathognomonic. However, few high-resolution analyses have been performed and focal DNA copy number changes with corresponding candidate target genes remain poorly described for individual subtypes. We present the first high-resolution DNA copy number aberration (CNA) analysis on the subtype embryonal carcinomas (ECs), including 13 primary ECs and 5 EC cell lines. We identified recurrent gains and losses and allele-specific CNAs. Within these regions, we nominate 30 genes that may be of interest to the EC subtype. By in silico analysis of data from 150 TGCTs from The Cancer Genome Atlas (TCGA), we further investigated CNAs, RNA expression, somatic mutations and fusion transcripts of these genes. Among primary ECs, ploidy ranged between 2.3 and 5.0, and the most common aberrations were DNA copy number gains at chromosome (arm) 7, 8, 12p, and 17, losses at 4, 10, 11, and 18, replicating known TGCT genome characteristics. Gain of whole or parts of 12p was found in all samples, including a highly amplified 100 kbp segment at 12p13.31, containing SLC2A3. Gain at 7p21, encompassing ETV1, was the second most frequent aberration. In conclusion, we present novel CNAs and the genes located within these regions, where the copy number gain of SLC2A3 and ETV1 are of interest, and which copy number levels also correlate with expression in TGCTs.