Comprehensive Analysis of BRCA1, BRCA2 and TP53 Germline Mutation and Tumor Characterization: A Portrait of Early-Onset Breast Cancer in Brazil

Carregando...
Imagem de Miniatura
Citações na Scopus
68
Tipo de produção
article
Data de publicação
2013
Título da Revista
ISSN da Revista
Título do Volume
Editora
PUBLIC LIBRARY SCIENCE
Autores
CARRARO, Dirce Maria
LISBOA, Bianca Cristina Garcia
OLIVIERI, Eloisa Helena Ribeiro
KREPISCHI, Ana Cristina Vitorino
CARVALHO, Alex Fiorini de
MOTA, Louise Danielle de Carvalho
PUGA, Renato David
MACIEL, Maria do Socorro
MICHELLI, Rodrigo Augusto Depieri
Citação
PLOS ONE, v.8, n.3, article ID e57581, 9p, 2013
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Germline mutations in BRCA1, BRCA2 and TP53 genes have been identified as one of the most important disease-causing issues in young breast cancer patients worldwide. The specific defective biological processes that trigger germline mutation-associated and -negative tumors remain unclear. To delineate an initial portrait of Brazilian early-onset breast cancer, we performed an investigation combining both germline and tumor analysis. Germline screening of the BRCA1, BRCA2, CHEK2 (c.1100delC) and TP53 genes was performed in 54 unrelated patients <35 y; their tumors were investigated with respect to transcriptional and genomic profiles as well as hormonal receptors and HER2 expression/amplification. Germline mutations were detected in 12 out of 54 patients (22%) [7 in BRCA1 (13%), 4 in BRCA2 (7%) and one in TP53 (2%) gene]. A cancer familial history was present in 31.4% of the unrelated patients, from them 43.7% were carriers for germline mutation (37.5% in BRCA1 and in 6.2% in the BRCA2 genes). Fifty percent of the unrelated patients with hormone receptor-negative tumors carried BRCA1 mutations, percentage increasing to 83% in cases with familial history of cancer. Over-representation of DNA damage-, cellular and cell cycle-related processes was detected in the up-regulated genes of BRCA1/2-associated tumors, whereas cell and embryo development-related processes were over-represented in the up-regulated genes of BRCA1/2-negative tumors, suggesting distinct mechanisms driving the tumorigenesis. An initial portrait of the early-onset breast cancer patients in Brazil was generated pointing out that hormone receptor-negative tumors and positive familial history are two major risk factors for detection of a BRCA1 germline mutation. Additionally, the data revealed molecular factors that potentially trigger the tumor development in young patients.
Palavras-chave
Referências
  1. Achatz MIW, 2007, CANCER LETT, V245, P96, DOI 10.1016/j.canlet.2005.12.039
  2. Anders CK, 2011, CANCER-AM CANCER SOC, V117, P1602, DOI 10.1002/cncr.25746
  3. Anders CK, 2008, J CLIN ONCOL, V26, P3324, DOI 10.1200/JCO.2007.14.2471
  4. Azim HA, 2012, CLIN CANCER RES, V18, P1341, DOI 10.1158/1078-0432.CCR-11-2599
  5. Bacchi LM, 2010, BREAST, V19, P137, DOI 10.1016/j.breast.2010.01.002
  6. Bayraktar S, 2011, BREAST CANCER RES TR, V130, P145, DOI 10.1007/s10549-011-1711-z
  7. Bonadona V, 2005, GENE CHROMOSOME CANC, V43, P404, DOI 10.1002/gcc.20199
  8. Bos PD, 2009, NATURE, V459, P1005, DOI 10.1038/nature08021
  9. Brekelmans CTM, 2007, EUR J CANCER, V43, P867, DOI 10.1016/j.ejca.2006.12.009
  10. Cabodi S, 2010, NAT REV CANCER, V10, P858, DOI 10.1038/nrc2967
  11. Cancello G, 2010, ANN ONCOL, V21, P1974, DOI 10.1093/annonc/mdq072
  12. Carey LA, 2006, JAMA-J AM MED ASSOC, V295, P2492, DOI 10.1001/jama.295.21.2492
  13. Carvalho Leda Viegas de, 2010, Rev Assoc Med Bras, V56, P278
  14. Castro NP, 2008, BREAST CANCER RES, V10, DOI 10.1186/bcr2157
  15. Colleoni M, 2002, ANN ONCOL, V13, P273, DOI 10.1093/annonc/mdf039
  16. da Costa ECB, 2008, CANCER GENET CYTOGEN, V184, P62, DOI 10.1016/j.cancergencyto.2008.03.011
  17. Damiano L, 2010, ONCOGENE, V29, P3677, DOI 10.1038/onc.2010.128
  18. Dutra Mara Costa, 2009, Rev Bras Ginecol Obstet, V31, P54, DOI 10.1590/S0100-72032009000200002
  19. El Saghir NS, 2006, BMC CANCER, V6, DOI 10.1186/1471-2407-6-194
  20. Fackenthal JD, 2007, NAT REV CANCER, V7, P937, DOI 10.1038/nrc2054
  21. Fernandopulle SM, 2006, PATHOLOGY, V38, P219, DOI 10.1080/00313020600699268
  22. Figueiredo JC, 2007, BREAST CANCER RES TR, V105, P69, DOI 10.1007/s10549-006-9433-3
  23. Folgueira MAAK, 2005, CLIN CANCER RES, V11, P7434
  24. Garritano S, 2010, HUM MUTAT, V31, P143, DOI 10.1002/humu.21151
  25. Gentilini O, 2010, BREAST, V19, P55, DOI 10.1016/j.breast.2009.11.001
  26. Ginsburg OM, 2009, FAM CANCER, V8, P563, DOI 10.1007/s10689-009-9287-z
  27. Gomes MCB, 2007, BREAST CANCER RES TR, V103, P349, DOI 10.1007/s10549-006-9378-6
  28. Gonzalez-Angulo AM, 2005, CANCER, V103, P2466, DOI 10.1002/cncr.21070
  29. Haffty BG, 2009, ANN ONCOL, V20, P1653, DOI 10.1093/annonc/mdp051
  30. Han W, 2010, BREAST CANCER RES TR, V119, P193, DOI 10.1007/s10549-009-0388-z
  31. Hayashi T, 2004, J AM COLL CARDIOL, V44, P2192, DOI 10.1016/j.jacc.2004.08.058
  32. Hedenfalk I, 2003, P NATL ACAD SCI USA, V100, P2532, DOI 10.1073/pnas.0533805100
  33. Jacome GPO, 2010, J TOXICOL ENV HEAL A, V73, P858, DOI 10.1080/15287391003744773
  34. Jonsson G, 2005, CANCER RES, V65, P7612, DOI 10.1158/0008-5472.CAN-05-0570
  35. Krepischi ACV, 2012, BREAST CANCER RES, V14, DOI 10.1186/bcr3109
  36. Lakhani SR, 2000, CLIN CANCER RES, V6, P782
  37. Lalloo F, 2006, EUR J CANCER, V42, P1143, DOI 10.1016/j.ejca.2005.11.032
  38. Loizidou M, 2007, CLIN GENET, V71, P165, DOI 10.1111/j.1399-0004.2007.00747.x
  39. Lourenco JJ, 2004, GENET MOL BIOL, V27, P500, DOI 10.1590/S1415-47572004000400006
  40. Oldenburg RA, 2006, CLIN CANCER RES, V12, P1693, DOI 10.1158/1078-0432.CCR-05-2230
  41. Palacios J, 2005, BREAST CANCER RES TR, V90, P5, DOI 10.1007/s10549-004-1536-0
  42. Parker JS, 2009, J CLIN ONCOL, V27, P1160, DOI 10.1200/JCO.2008.18.1370
  43. Peng RJ, 2011, BREAST, V20, P568, DOI 10.1016/j.breast.2011.07.012
  44. Perou CM, 2000, NATURE, V406, P747, DOI 10.1038/35021093
  45. Young SR, 2009, BMC CANCER, V9, DOI 10.1186/1471-2407-9-86
  46. Robertson L, 2012, BRIT J CANCER, V106, P1234, DOI 10.1038/bjc.2012.31
  47. Sidoni A, 2003, BREAST, V12, P247, DOI 10.1016/S0960-9776(03)00095-X
  48. Sorlie T, 2001, P NATL ACAD SCI USA, V98, P10869, DOI 10.1073/pnas.191367098
  49. Uhrhammer Nancy, 2008, Int J Med Sci, V5, P197
  50. Walsh T, 2007, CANCER CELL, V11, P103, DOI 10.1016/j.ccr.2007.01.010