PMID- 29659569
OWN - NLM
STAT- MEDLINE
DCOM- 20180619
LR  - 20181114
IS  - 1553-7404 (Electronic)
IS  - 1553-7390 (Linking)
VI  - 14
IP  - 4
DP  - 2018 Apr
TI  - Targeted next generation sequencing identifies functionally deleterious germline 
      mutations in novel genes in early-onset/familial prostate cancer.
PG  - e1007355
LID - 10.1371/journal.pgen.1007355 [doi]
AB  - Considering that mutations in known prostate cancer (PrCa) predisposition genes, 
      including those responsible for hereditary breast/ovarian cancer and Lynch
      syndromes, explain less than 5% of early-onset/familial PrCa, we have sequenced
      94 genes associated with cancer predisposition using next generation sequencing
      (NGS) in a series of 121 PrCa patients. We found monoallelic
      truncating/functionally deleterious mutations in seven genes, including ATM and
      CHEK2, which have previously been associated with PrCa predisposition, and five
      new candidate PrCa associated genes involved in cancer predisposing recessive
      disorders, namely RAD51C, FANCD2, FANCI, CEP57 and RECQL4. Furthermore, using in 
      silico pathogenicity prediction of missense variants among 18 genes associated
      with breast/ovarian cancer and/or Lynch syndrome, followed by KASP genotyping in 
      710 healthy controls, we identified "likely pathogenic" missense variants in ATM,
      BRIP1, CHEK2 and TP53. In conclusion, this study has identified putative PrCa
      predisposing germline mutations in 14.9% of early-onset/familial PrCa patients.
      Further data will be necessary to confirm the genetic heterogeneity of inherited 
      PrCa predisposition hinted in this study.
FAU - Paulo, Paula
AU  - Paulo P
AUID- ORCID: 0000-0001-8387-2127
AD  - Cancer Genetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology
      Institute of Porto (IPO Porto), Porto, Portugal.
FAU - Maia, Sofia
AU  - Maia S
AD  - Cancer Genetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology
      Institute of Porto (IPO Porto), Porto, Portugal.
FAU - Pinto, Carla
AU  - Pinto C
AD  - Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto),
      Porto, Portugal.
FAU - Pinto, Pedro
AU  - Pinto P
AD  - Cancer Genetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology
      Institute of Porto (IPO Porto), Porto, Portugal.
FAU - Monteiro, Augusta
AU  - Monteiro A
AD  - Cancer Genetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology
      Institute of Porto (IPO Porto), Porto, Portugal.
FAU - Peixoto, Ana
AU  - Peixoto A
AD  - Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto),
      Porto, Portugal.
FAU - Teixeira, Manuel R
AU  - Teixeira MR
AUID- ORCID: 0000-0002-3633-1659
AD  - Cancer Genetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology
      Institute of Porto (IPO Porto), Porto, Portugal.
AD  - Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto),
      Porto, Portugal.
AD  - Biomedical Sciences Institute Abel Salazar (ICBAS), University of Porto, Porto,
      Portugal.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180416
PL  - United States
TA  - PLoS Genet
JT  - PLoS genetics
JID - 101239074
RN  - 0 (CEP57 protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (FANCD2 protein, human)
RN  - 0 (FANCI protein, human)
RN  - 0 (Fanconi Anemia Complementation Group D2 Protein)
RN  - 0 (Fanconi Anemia Complementation Group Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RAD51C protein, human)
RN  - EC 2.7.1.11 (Checkpoint Kinase 2)
RN  - EC 2.7.11.1 (ATM protein, human)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
RN  - EC 2.7.11.1 (CHEK2 protein, human)
RN  - EC 3.6.1.- (RECQL4 protein, human)
RN  - EC 3.6.4.12 (RecQ Helicases)
RN  - EC 3.6.4.13 (BRIP1 protein, human)
RN  - EC 3.6.4.13 (RNA Helicases)
RN  - Prostate cancer, familial
SB  - IM
MH  - Adult
MH  - Age of Onset
MH  - Ataxia Telangiectasia Mutated Proteins/genetics
MH  - Breast Neoplasms/genetics
MH  - Case-Control Studies
MH  - Checkpoint Kinase 2/genetics
MH  - Colorectal Neoplasms, Hereditary Nonpolyposis/genetics
MH  - Computer Simulation
MH  - DNA-Binding Proteins/genetics
MH  - Fanconi Anemia Complementation Group D2 Protein/genetics
MH  - Fanconi Anemia Complementation Group Proteins/genetics
MH  - Female
MH  - Genes, p53
MH  - Genetic Predisposition to Disease
MH  - Genetic Variation
MH  - *Germ-Line Mutation
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Male
MH  - Microtubule-Associated Proteins/genetics
MH  - Middle Aged
MH  - Mutation, Missense
MH  - Nuclear Proteins/genetics
MH  - Ovarian Neoplasms/genetics
MH  - Pedigree
MH  - Prostatic Neoplasms/*genetics
MH  - RNA Helicases/genetics
MH  - RecQ Helicases/genetics
MH  - Sequence Analysis, DNA
PMC - PMC5919682
EDAT- 2018/04/17 06:00
MHDA- 2018/06/21 06:00
CRDT- 2018/04/17 06:00
PHST- 2017/03/15 00:00 [received]
PHST- 2018/04/05 00:00 [accepted]
PHST- 2018/04/26 00:00 [revised]
PHST- 2018/04/17 06:00 [pubmed]
PHST- 2018/06/21 06:00 [medline]
PHST- 2018/04/17 06:00 [entrez]
AID - 10.1371/journal.pgen.1007355 [doi]
AID - PGENETICS-D-17-00545 [pii]
PST - epublish
SO  - PLoS Genet. 2018 Apr 16;14(4):e1007355. doi: 10.1371/journal.pgen.1007355.
      eCollection 2018 Apr.