ABSTRACT
Recently mutations in the MED12 gene have been reported in 5.4% of prostate tumours from Caucasian patients analysed by exome sequencing (Barbieri CE, Baca SC, Lawrence MS, et al. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nature Genet 2012; 44: 685-689). In more than 70% of prostate tumours with MED12 mutation, a recurrent p.L1224F mutation in exon 26 was found. In order to validate this MED12 p.L1224F mutation, an unselected cohort of prostate tumours from Caucasian patients was analysed by Sanger sequencing. Overall, 223 prostate tumours and three lymph node metastases were analysed. The MED12 p.L1224F mutation could not be detected in any of the cases. So far, the recently reported MED12 p.L1224F mutation could not be validated in our unselected cohort of prostate tumours. Contrary to the findings of Barbieri et al, our data indicate either that the p.L1224F mutation in the MED12 gene plays no role in prostate carcinogenesis or that this alteration is only relevant in a small subgroup of tumours.
Subject(s)
Mediator Complex/genetics , Mutation , Prostatic Neoplasms/genetics , White People/genetics , DNA Mutational Analysis , Genetic Predisposition to Disease , Germany/epidemiology , Humans , Lymphatic Metastasis , Male , Mutation Rate , Phenotype , Prostatic Neoplasms/ethnology , Prostatic Neoplasms/pathologyABSTRACT
PURPOSE: The deleted-in-polyposis1-like1 (DP1L1) gene displays pro-apoptotic activity and was proposed to be a tumor suppressor. It locates on chromosome 19p13.3, which harbors the locus for Peutz-Jeghers-Syndrome and is deleted in various tumors. We analyzed the association of DP1L1 polymorphisms with colon cancer, and cancer-associated Ulcerative colitis and Crohn's disease. EXPERIMENTAL DESIGN: Fifty-eight patients with colon cancer, 18 with Ulcerative colitis, 18 with Crohn's disease, and 70 control individuals were genotyped for SNPs at positions 992 and 996 of DP1L1 cDNA. RESULTS: Homozygous carriers of 992A alleles comprised 16% of the control group but were significantly increased in colon cancer with a frequency of 36% (P = 0.013 cancer vs control). Homozygous 991-A was also elevated in Ulcerative colitis (N = 18) with a frequency of 33%. In contrast, 18 patients with Crohn's disease showed no difference in frequency of 992AA (22%) compared to control. The A-allele of the adjacent C996A polymorphism has a low frequency (3.5%) in the control population, but significantly increased frequency of 13% in colon cancer (P = 0.0149 for allele frequency, Fisher's exact). 996-A allele frequency is also increased in inflammatory bowel disease (IBD): 22% of Ulcerative colitis- and 50% of Crohn's disease-patients were heterozygous carriers of 996-A (P = 0.052 for CU and P < 0.0001 for MC vs controls). CONCLUSIONS: DP1L1 polymorphisms are associated with colon cancer and IBD. This indicates that DP1L1 plays a functional role in these conditions. Thus DP1L1 may be a diagnostic and therapeutic target for colon cancer and IBD.
