title: Identification of Two Novel HOXB13 Germline Mutations in Portuguese Prostate Cancer Patients.
abstract: The HOXB13 germline variant G84E (rs138213197) was recently described in men of European descent, with the highest prevalence in Northern Europe. The G84E mutation has not been found in patients of African or Asian ancestry, which may carry other HOXB13 variants, indicating allelic heterogeneity depending on the population. In order to gain insight into the full scope of coding HOXB13 mutations in Portuguese prostate cancer patients, we decided to sequence the entire coding region of the HOXB13 gene in 462 early-onset or familial/hereditary cases. Additionally, we searched for somatic HOXB13 mutations in 178 prostate carcinomas to evaluate their prevalence in prostate carcinogenesis. Three different patients were found to carry in their germline DNA two novel missense variants, which were not identified in 132 control subjects. Both variants are predicted to be deleterious by different in silico tools. No somatic mutations were found. These findings further support the hypothesis that different rare HOXB13 mutations may be found in different ethnic groups. Detection of mutations predisposing to prostate cancer may require re-sequencing rather than genotyping, as appropriate to the population under investigation.
authors.affiliation: Department of Genetics and Cancer Genetics Group-CI-IPOP, Portuguese Oncology Institute-Porto, Porto, Portugal.
authors.forename: Sofia
authors.initials: S
authors.lastname: Maia
authors.affiliation: Department of Genetics and Cancer Genetics Group-CI-IPOP, Portuguese Oncology Institute-Porto, Porto, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Cardoso
authors.affiliation: Department of Genetics and Cancer Genetics Group-CI-IPOP, Portuguese Oncology Institute-Porto, Porto, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Pinto
authors.affiliation: Department of Genetics and Cancer Genetics Group-CI-IPOP, Portuguese Oncology Institute-Porto, Porto, Portugal.
authors.forename: Manuela
authors.initials: M
authors.lastname: Pinheiro
authors.affiliation: Department of Genetics and Cancer Genetics Group-CI-IPOP, Portuguese Oncology Institute-Porto, Porto, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Santos
authors.affiliation: Department of Genetics and Cancer Genetics Group-CI-IPOP, Portuguese Oncology Institute-Porto, Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Peixoto
authors.affiliation: Department of Epidemiology, Portuguese Oncology Institute-Porto, Porto, Portugal; North Region Cancer Registry, Portuguese Oncology Institute-Porto, Porto, Portugal; Biomedical Sciences Institute (ICBAS), University of Porto-Porto, Portugal.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Bento
authors.affiliation: Department of Urology, Portuguese Oncology Institute-Porto, Porto, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Oliveira
authors.affiliation: Biomedical Sciences Institute (ICBAS), University of Porto-Porto, Portugal; Cancer Biology and Epigenetics Group-CI-IPOP, Portuguese Oncology Institute-Porto, Porto, Portugal; Department of Pathology, Portuguese Oncology Institute-Porto, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.affiliation: Biomedical Sciences Institute (ICBAS), University of Porto-Porto, Portugal; Cancer Biology and Epigenetics Group-CI-IPOP, Portuguese Oncology Institute-Porto, Porto, Portugal.
authors.forename: Carmen
authors.initials: C
authors.lastname: Jerónimo
authors.affiliation: Department of Genetics and Cancer Genetics Group-CI-IPOP, Portuguese Oncology Institute-Porto, Porto, Portugal; Biomedical Sciences Institute (ICBAS), University of Porto-Porto, Portugal.
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D011174:Portugal; D015995:Prevalence; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors
chemical_list: C484414:HOXB13 protein, human; D018398:Homeodomain Proteins