دورية أكاديمية
Germline variants in DNA repair genes associated with hereditary breast and ovarian cancer syndrome: analysis of a 21 gene panel in the Brazilian population.
العنوان: | Germline variants in DNA repair genes associated with hereditary breast and ovarian cancer syndrome: analysis of a 21 gene panel in the Brazilian population. |
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المؤلفون: | da Costa E Silva Carvalho S; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.; Center for Medical Genomics at University Hospital of the Ribeirão Preto Medical School of University of São Paulo, Ribeirão Preto, SP, Brazil.; Regional Blood Center at University Hospital of the Ribeirão Preto Medical School of University of São Paulo, Ribeirão Preto, SP, Brazil., Cury NM; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.; Regional Blood Center at University Hospital of the Ribeirão Preto Medical School of University of São Paulo, Ribeirão Preto, SP, Brazil., Brotto DB; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.; Regional Blood Center at University Hospital of the Ribeirão Preto Medical School of University of São Paulo, Ribeirão Preto, SP, Brazil., de Araujo LF; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.; Regional Blood Center at University Hospital of the Ribeirão Preto Medical School of University of São Paulo, Ribeirão Preto, SP, Brazil., Rosa RCA; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.; Center for Medical Genomics at University Hospital of the Ribeirão Preto Medical School of University of São Paulo, Ribeirão Preto, SP, Brazil., Texeira LA; Division of Internal Medicine and Geriatrics, Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil., Plaça JR; Regional Blood Center at University Hospital of the Ribeirão Preto Medical School of University of São Paulo, Ribeirão Preto, SP, Brazil., Marques AA; Regional Blood Center at University Hospital of the Ribeirão Preto Medical School of University of São Paulo, Ribeirão Preto, SP, Brazil., Peronni KC; Regional Blood Center at University Hospital of the Ribeirão Preto Medical School of University of São Paulo, Ribeirão Preto, SP, Brazil., Ruy PC; Center for Medical Genomics at University Hospital of the Ribeirão Preto Medical School of University of São Paulo, Ribeirão Preto, SP, Brazil., Molfetta GA; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.; Center for Medical Genomics at University Hospital of the Ribeirão Preto Medical School of University of São Paulo, Ribeirão Preto, SP, Brazil., Moriguti JC; Division of Internal Medicine and Geriatrics, Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil., Carraro DM; International Research, Center/CIPE, AC Camargo Cancer Center, Sao Paulo, SP, Brazil., Palmero EI; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil., Ashton-Prolla P; Laboratório de Medicina Genômica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil., de Faria Ferraz VE; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.; Center for Medical Genomics at University Hospital of the Ribeirão Preto Medical School of University of São Paulo, Ribeirão Preto, SP, Brazil.; Department of Medical Genetics, University Hospital of the Ribeirão Preto Medical School, Ribeirão Preto, Brazil., Silva WA Jr; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. wilsonjr@usp.br.; Center for Medical Genomics at University Hospital of the Ribeirão Preto Medical School of University of São Paulo, Ribeirão Preto, SP, Brazil. wilsonjr@usp.br.; Regional Blood Center at University Hospital of the Ribeirão Preto Medical School of University of São Paulo, Ribeirão Preto, SP, Brazil. wilsonjr@usp.br. |
المصدر: | BMC medical genomics [BMC Med Genomics] 2020 Feb 10; Vol. 13 (1), pp. 21. Date of Electronic Publication: 2020 Feb 10. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101319628 Publication Model: Electronic Cited Medium: Internet ISSN: 1755-8794 (Electronic) Linking ISSN: 17558794 NLM ISO Abbreviation: BMC Med Genomics Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : BioMed Central |
مواضيع طبية MeSH: | Algorithms* , Computer Simulation* , Germ-Line Mutation* , INDEL Mutation*, Hereditary Breast and Ovarian Cancer Syndrome/*genetics , Neoplasm Proteins/*genetics, Adult ; Aged ; Brazil ; Female ; Humans ; Middle Aged |
مستخلص: | Background: The Hereditary Breast and Ovarian Cancer Syndrome (HBOC) occurs in families with a history of breast/ovarian cancer, presenting an autosomal dominant inheritance pattern. BRCA1 and BRCA2 are high penetrance genes associated with an increased risk of up to 20-fold for breast and ovarian cancer. However, only 20-30% of HBOC cases present pathogenic variants in those genes, and other DNA repair genes have emerged as increasing the risk for HBOC. In Brazil, variants in ATM, ATR, CHEK2, MLH1, MSH2, MSH6, POLQ, PTEN, and TP53 genes have been reported in up to 7.35% of the studied cases. Here we screened and characterized variants in 21 DNA repair genes in HBOC patients. Methods: We systematically analyzed 708 amplicons encompassing the coding and flanking regions of 21 genes related to DNA repair pathways (ABRAXAS1, ATM, ATR, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MLH1, MRE11, MSH2, MSH6, NBN, PALB2, PMS2, PTEN, RAD50, RAD51, TP53 and UIMC1). A total of 95 individuals with HBOC syndrome clinical suspicion in Southeast Brazil were sequenced, and 25 samples were evaluated for insertions/deletions in BRCA1/BRCA2 genes. Identified variants were assessed in terms of population allele frequency and their functional effects were predicted through in silico algorithms. Results: We identified 80 variants in 19 genes. About 23.4% of the patients presented pathogenic variants in BRCA1, BRCA2 and TP53, a frequency higher than that identified among previous studies in Brazil. We identified a novel variant in ATR, which was predicted as pathogenic by in silico tools. The association analysis revealed 13 missense variants in ABRAXAS1, BARD1, BRCA2, CHEK2, CDH1, MLH1, PALB2, and PMS2 genes, as significantly associated with increased risk to HBOC, and the patients carrying those variants did not present large insertions or deletions in BRCA1/BRCA2 genes. Conclusions: This study embodies the third report of a multi-gene analysis in the Brazilian population, and addresses the first report of many germline variants associated with HBOC in Brazil. Although further functional analyses are necessary to better characterize the contribution of those variants to the phenotype, these findings would improve the risk estimation and clinical follow-up of patients with HBOC clinical suspicion. |
References: | PLoS One. 2014 Apr 11;9(4):e94554. (PMID: 24728327) Oncogene. 2017 Jul 20;36(29):4161-4170. (PMID: 28319063) Mol Cell. 2009 Sep 24;35(6):818-29. (PMID: 19782031) Science. 2007 May 25;316(5828):1202-5. (PMID: 17525342) Sci Rep. 2018 Oct 15;8(1):15263. (PMID: 30323354) Hum Mutat. 2009 Jun;30(6):952-9. (PMID: 19370756) PLoS One. 2018 Dec 31;13(12):e0209934. (PMID: 30596752) Trends Biochem Sci. 2019 Mar;44(3):226-240. (PMID: 30638972) Biochimie. 2018 Mar;146:87-96. (PMID: 29175432) Cell Oncol (Dordr). 2011 Apr;34(2):71-88. (PMID: 21336636) Exp Cell Res. 2009 May 1;315(8):1393-402. (PMID: 19268661) Curr Probl Cancer. 2017 Jul - Aug;41(4):251-264. (PMID: 28454847) Cancers (Basel). 2018 Dec 19;10(12):. (PMID: 30572612) J Cancer Res Clin Oncol. 2018 Dec;144(12):2495-2513. (PMID: 30306255) Nature. 2012 Nov 1;491(7422):56-65. (PMID: 23128226) Genes (Basel). 2017 Dec 08;8(12):. (PMID: 29292755) Gynecol Oncol. 2019 May;153(2):452-462. (PMID: 30733081) Oncotarget. 2017 Jul 18;8(29):47064-47075. (PMID: 28423363) Bioinformatics. 2016 Oct 1;32(19):3012-4. (PMID: 27288499) Oncotarget. 2019 Jan 18;10(6):631-632. (PMID: 30774760) Nucleic Acids Res. 2003 Jul 1;31(13):3812-4. (PMID: 12824425) Breast Cancer Res Treat. 2011 Jul;128(1):293-4; author reply 295. (PMID: 21327466) BMC Cancer. 2016 Dec 3;16(1):934. (PMID: 27914478) Cancer. 2017 May 15;123(10):1721-1730. (PMID: 28085182) Hum Mol Genet. 2012 Jun 15;21(12):2738-44. (PMID: 22419737) Gynecol Oncol. 2015 Apr;137(1):86-92. (PMID: 25622547) Front Genet. 2018 May 07;9:161. (PMID: 29868112) Int J Cancer. 2007 Dec 15;121(12):2661-7. (PMID: 17721994) Mol Cell. 2016 Feb 4;61(3):434-448. (PMID: 26778126) Nucleic Acids Res. 2019 Nov 18;47(20):10662-10677. (PMID: 31586400) Cancer Biol Ther. 2017 Jul 3;18(7):519-533. (PMID: 28494185) Oncogene. 2005 May 26;24(23):3726-36. (PMID: 15782130) Surg Oncol. 2015 Jun;24(2):100-9. (PMID: 25936246) BMC Cancer. 2019 Jan 3;19(1):4. (PMID: 30606148) Hum Mutat. 2008 Nov;29(11):1342-54. (PMID: 18951461) Breast Cancer. 2019 May;26(3):397-405. (PMID: 30535581) Oncotarget. 2016 Dec 6;7(49):80465-80481. (PMID: 27741520) PLoS One. 2011 Feb 16;6(2):e17063. (PMID: 21359226) Ann Oncol. 2014 May;25(5):1004-11. (PMID: 24562447) JAMA. 2006 May 24;295(20):2374-84. (PMID: 16720823) Breast Cancer Res Treat. 2015 Jul;152(1):129-136. (PMID: 26022348) Nat Commun. 2017 Jun 01;8:15752. (PMID: 28569838) Prostate. 2014 Oct;74(14):1444-51. (PMID: 25111659) J Clin Oncol. 2016 May 1;34(13):1460-8. (PMID: 26976419) Nat Commun. 2016 Sep 15;7:12813. (PMID: 27628236) Ann Surg Oncol. 2015 Oct;22(10):3282-8. (PMID: 26219241) Int J Mol Sci. 2017 Aug 31;18(9):. (PMID: 28858227) PLoS Genet. 2019 Mar 29;15(3):e1008049. (PMID: 30925164) J Mol Cell Biol. 2014 Dec;6(6):442-57. (PMID: 25404613) Int J Cancer. 2019 Jun 1;144(11):2683-2694. (PMID: 30426508) PLoS One. 2016 Jun 07;11(6):e0156820. (PMID: 27270457) Bioinformatics. 2016 Sep 15;32(18):2847-9. (PMID: 27207943) Genet Med. 2015 May;17(5):405-24. (PMID: 25741868) Genes Dev. 2009 Mar 15;23(6):729-39. (PMID: 19261749) Eur J Hum Genet. 2014 Nov;22(11):1305-13. (PMID: 24549055) Nature. 1995 Dec 21-28;378(6559):789-92. (PMID: 8524414) Breast Cancer Res. 2011;13(6):R119. (PMID: 22114986) Mol Genet Genomic Med. 2015 Sep;3(5):459-66. (PMID: 26436112) Tumour Biol. 2017 Feb;39(2):1010428317694303. (PMID: 28231738) Eur J Hum Genet. 2011 Mar;19(3):300-6. (PMID: 21119707) Cancers (Basel). 2018 Sep 27;10(10):. (PMID: 30262796) Breast Cancer Res Treat. 2018 Dec;172(3):637-646. (PMID: 30159786) Hum Mutat. 2005 Sep;26(3):284. (PMID: 16088935) Nat Methods. 2014 Apr;11(4):361-2. (PMID: 24681721) Nat Genet. 2014 Mar;46(3):310-5. (PMID: 24487276) Nature. 2015 Oct 1;526(7571):68-74. (PMID: 26432245) BMC Med Genet. 2014 May 15;15:55. (PMID: 24884479) Science. 2002 Sep 13;297(5588):1837-48. (PMID: 12228710) Cancer Prev Res (Phila). 2017 Oct;10(10):580-587. (PMID: 28765196) Br Med Bull. 2014 Dec;112(1):57-69. (PMID: 25473022) Nature. 2019 Jul;571(7763):27-29. (PMID: 31270479) Hered Cancer Clin Pract. 2016 Jul 12;14:14. (PMID: 27413415) J Clin Oncol. 2017 Aug 1;35(22):2568-2575. (PMID: 28514183) Genet Mol Biol. 2016 May 24;39(2):210-22. (PMID: 27223485) Nat Rev Cancer. 2011 Dec 23;12(1):68-78. (PMID: 22193408) Cell Rep. 2014 Aug 7;8(3):807-17. (PMID: 25066119) Science. 1994 Oct 7;266(5182):66-71. (PMID: 7545954) J Med Genet. 2004 Sep;41(9):e114. (PMID: 15342711) Acta Biochim Biophys Sin (Shanghai). 2016 Jul;48(7):658-64. (PMID: 27325824) Science. 2014 Mar 28;343(6178):1466-70. (PMID: 24675953) Science. 1990 Dec 21;250(4988):1684-9. (PMID: 2270482) Cancer Genet. 2018 Dec;228-229:93-97. (PMID: 30553478) Biomed Res Int. 2015;2015:341723. (PMID: 26075229) Hum Mutat. 2017 Jul;38(7):751-763. (PMID: 28332257) Genet Mol Biol. 2019;42(1 suppl 1):215-231. (PMID: 31067289) Bioinformatics. 2019 Jun 1;35(11):1978-1980. (PMID: 30376034) Hum Mol Genet. 2003 Nov 15;12(22):3007-16. (PMID: 14500541) Cancer Res. 2018 Sep 15;78(18):5375-5383. (PMID: 30042151) Cancer Res. 2006 Sep 15;66(18):8966-70. (PMID: 16982735) Oncogene. 2004 Nov 4;23(52):8411-8. (PMID: 15361833) Gene. 2015 Sep 1;568(2):215-9. (PMID: 25981591) Hered Cancer Clin Pract. 2014 Mar 13;12(1):8. (PMID: 24625245) Ann Oncol. 2013 Nov;24 Suppl 8:viii83-viii95. (PMID: 24131978) Fam Cancer. 2017 Oct;16(4):501-507. (PMID: 28365877) |
فهرسة مساهمة: | Keywords: BRCA1; BRCA2; DNA repair genes; HBOC; Molecular diagnosis; Multi-gene panel screening; Next-generation sequencing |
المشرفين على المادة: | 0 (Neoplasm Proteins) |
تواريخ الأحداث: | Date Created: 20200211 Date Completed: 20201216 Latest Revision: 20240627 |
رمز التحديث: | 20240627 |
مُعرف محوري في PubMed: | PMC7011249 |
DOI: | 10.1186/s12920-019-0652-y |
PMID: | 32039725 |
قاعدة البيانات: | MEDLINE |
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