nach oben

Erschienen in:

01.12.2010

Comprehensive BRCA1 and BRCA2 mutation analyses and review of French Canadian families with at least three cases of breast cancer

verfasst von: Luca Cavallone, Suzanna L. Arcand, Christine M. Maugard, Serge Nolet, Louis A. Gaboury, Anne-Marie Mes-Masson, Parviz Ghadirian, Diane Provencher, Patricia N. Tonin

Erschienen in: Familial Cancer | Ausgabe 4/2010

Einloggen, um Zugang zu erhalten

Abstract

Few studies have reported on the comprehensive BRCA1/2 mutation analyses of hereditary breast cancer (HBC) families of French Canadian descent. Here we report the investigation of 82 families with at least 3 cases of breast cancer evaluated for mutations by DNA sequencing and/or multiplex ligation-dependent probe amplification (MLPA) assay. DNA sequencing identified pathogenic mutations in 37 (45.1%) families, of which 70.2% were one of three recurring mutations (BRCA1:R1443X, BRCA2:8765delAG, and BRCA2:E1953X) frequently reported in this founder population; and variants of uncertain clinical significance in 7 (8.5%) families of which two harbored BRCA2:E3002K. MLPA analysis of the 38 DNA sequence-negative families did not reveal any large rearrangements in BRCA1/2. A phenotypic characterization of the cancer families based on pathogenic mutation status revealed that there were significantly fewer very young age at diagnosis breast cancer cases (<36 years) in mutation-negative families (5.9%, 9 of 153) than in BRCA1 (22.8%, 13 of 57; P = 0.0003) or BRCA2 (22.9%, 27 of 118; P < 1× 10E5) mutation-positive families. There were significantly more mutation-positive families (29 of 36, 80.6%) with a very young age of onset of breast cancer case than those that did not (8 of 39, 20.5%) (P < 10E6). The comprehensive mutation analysis of BRCA1/2 suggests that genomic rearrangements are unlikely to account for sequence-negative HBC families and affirms that the presence of a very young age of diagnosis of breast cancer is strongly predictive of mutation carrier status of French Canadian HBC families.

Nur mit Berechtigung zugänglich

Tonin PN (2006) The limited spectrum of pathogenic BRCA1 and BRCA2 mutations in the French Canadian breast and breast-ovarian cancer families, a founder population of Quebec, Canada. Bull Cancer 93(9):841–846PubMed

Tonin PN, Mes-Masson AM, Futreal PA et al (1998) Founder BRCA1 and BRCA2 mutations in French Canadian breast and ovarian cancer families. Am J Hum Genet 63(5):1341–1351CrossRefPubMed

Oros KK, Ghadirian P, Greenwood CM et al (2004) Significant proportion of breast and/or ovarian cancer families of French Canadian descent harbor 1 of 5 BRCA1 and BRCA2 mutations. Int J Cancer 112(3):411–419CrossRefPubMed

Oros KK, Ghadirian P, Maugard CM et al (2006) Application of BRCA1 and BRCA2 mutation carrier prediction models in breast and/or ovarian cancer families of French Canadian descent. Clin Genet 70(4):320–329CrossRefPubMed

Simard J, Tonin P, Durocher F et al (1994) Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families. Nat Genet 8(4):392–398CrossRefPubMed

Manning AP, Abelovich D, Ghadirian P et al (2001) Haplotype analysis of BRCA2 8765delAG mutation carriers in French Canadian and Yemenite Jewish hereditary breast cancer families. Hum Hered 52(2):116–120CrossRefPubMed

Oros KK, Leblanc G, Arcand SL et al (2006) Haplotype analysis suggest common founders in carriers of the recurrent BRCA2 mutation, 3398delAAAAG, in French Canadian hereditary breast and/ovarian cancer families. BMC Med Genet 7:23CrossRefPubMed

Scriver CR (2001) Human genetics: lessons from Quebec populations. Annu Rev Genomics Hum Genet 2:69–101CrossRefPubMed

Laberge AM, Michaud J, Richter A et al (2005) Population history and its impact on medical genetics in Quebec. Clin Genet 68(4):287–301CrossRefPubMed

10.

Tonin PN, Maugard CM, Perret C, Mes-Masson AM, Provencher DM (2007) A review of histopathological subtypes of ovarian cancer in BRCA-related French Canadian cancer families. Fam Cancer 6(4):491–497CrossRefPubMed

11.

Gilks CB, Prat J (2009) Ovarian carcinoma pathology and genetics: recent advances. Hum Pathol 40(9):1213–1223CrossRefPubMed

12.

Simard J, Dumont M, Moisan AM et al (2007) Evaluation of BRCA1 and BRCA2 mutation prevalence, risk prediction models and a multistep testing approach in French-Canadian families with high risk of breast and ovarian cancer. J Med Genet 44(2):107–121CrossRefPubMed

13.

Pohlreich P, Zikan M, Stribrna J et al (2005) High proportion of recurrent germline mutations in the BRCA1 gene in breast and ovarian cancer patients from the Prague area. Breast Cancer Res 7(5):R728–R736CrossRefPubMed

14.

Hamann U, Liu X, Lange S, Ulmer HU, Benner A, Scott RJ (2002) Contribution of BRCA2 germline mutations to hereditary breast/ovarian cancer in Germany. J Med Genet 39(3):E12CrossRefPubMed

15.

Antoniou AC, Easton DF (2006) Models of genetic susceptibility to breast cancer. Oncogene 25(43):5898–5905CrossRefPubMed

16.

Antoniou AC, Easton DF (2006) Risk prediction models for familial breast cancer. Future Oncol 2(2):257–274CrossRefPubMed

17.

Smith P, McGuffog L, Easton DF et al (2006) A genome wide linkage search for breast cancer susceptibility genes. Genes Chromosomes Cancer 45(7):646–655CrossRefPubMed

18.

Houlston RS, Peto J (2004) The search for low-penetrance cancer susceptibility alleles. Oncogene 23(38):6471–6476CrossRefPubMed

19.

Guenard F, Labrie Y, Ouellette G, Joly Beauparlant C, Durocher F (2009) Genetic sequence variations of BRCA1-interacting genes AURKA, BAP1, BARD1 and DHX9 in French Canadian Families with high risk of breast cancer. J Hum Genet 54(3):152–161CrossRefPubMed

20.

Tischkowitz M, Xia B, Sabbaghian N et al (2007) Analysis of PALB2/FANCN-associated breast cancer families. Proc Natl Acad Sci U S A 104(16):6788–6793CrossRefPubMed

21.

Arcand SL, Maugard CM, Ghadirian P et al (2008) Germline TP53 mutations in BRCA1 and BRCA2 mutation-negative French Canadian breast cancer families. Breast Cancer Res Treat 108(3):399–408CrossRefPubMed

22.

Foulkes WD, Ghadirian P, Akbari MR et al (2007) Identification of a novel truncating PALB2 mutation and analysis of its contribution to early-onset breast cancer in French-Canadian women. Breast Cancer Res 9(6):R83CrossRefPubMed

23.

Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G (2002) Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 30(12):e57CrossRefPubMed

24.

Antoniou AC, Durocher F, Smith P, Simard J, Easton DF (2006) BRCA1 and BRCA2 mutation predictions using the BOADICEA and BRCAPRO models and penetrance estimation in high-risk French-Canadian families. Breast Cancer Res 8(1):R3CrossRefPubMed

25.

Moisan AM, Fortin J, Dumont M et al (2006) No Evidence of BRCA1/2 genomic rearrangements in high-risk French-Canadian breast/ovarian cancer families. Genet Test 10(2):104–115CrossRefPubMed

26.

Puget N, Torchard D, Serova-Sinilnikova OM et al (1997) A 1-kb Alu-mediated germ-line deletion removing BRCA1 exon 17. Cancer Res 57(5):828–831PubMed

27.

Petrij-Bosch A, Peelen T, van Vliet M et al (1997) BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients. Nat Genet 17(3):341–345CrossRefPubMed

28.

Vasickova P, Machackova E, Lukesova M et al (2007) High occurrence of BRCA1 intragenic rearrangements in hereditary breast and ovarian cancer syndrome in the Czech Republic. BMC Med Genet 8:32CrossRefPubMed

29.

Gad S, Aurias A, Puget N et al (2001) Color bar coding the BRCA1 gene on combed DNA: a useful strategy for detecting large gene rearrangements. Genes Chromosomes Cancer 31(1):75–84CrossRefPubMed

30.

Woodward AM, Davis TA, Silva AG, Kirk JA, Leary JA (2005) Large genomic rearrangements of both BRCA2 and BRCA1 are a feature of the inherited breast/ovarian cancer phenotype in selected families. J Med Genet 42(5):e31CrossRefPubMed

31.

Armaou S, Konstantopoulou I, Anagnostopoulos T et al (2007) Novel genomic rearrangements in the BRCA1 gene detected in Greek breast/ovarian cancer patients. Eur J Cancer 43(2):443–453CrossRefPubMed

32.

Lim YK, Lau PT, Ali AB et al (2007) Identification of novel BRCA large genomic rearrangements in Singapore Asian breast and ovarian patients with cancer. Clin Genet 71(4):331–342CrossRefPubMed

33.

Walsh T, Casadei S, Coats KH et al (2006) Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA 295(12):1379–1388CrossRefPubMed

34.

Puget N, Stoppa-Lyonnet D, Sinilnikova OM et al (1999) Screening for germ-line rearrangements and regulatory mutations in BRCA1 led to the identification of four new deletions. Cancer Res 59(2):455–461PubMed

35.

Mazoyer S (2005) Genomic rearrangements in the BRCA1 and BRCA2 genes. Hum Mutat 25(5):415–422CrossRefPubMed

36.

Montagna M, Dalla Palma M, Menin C et al (2003) Genomic rearrangements account for more than one-third of the BRCA1 mutations in northern Italian breast/ovarian cancer families. Hum Mol Genet 12(9):1055–1061CrossRefPubMed

37.

Ramus SJ, Harrington PA, Pye C et al (2007) Contribution of BRCA1 and BRCA2 mutations to inherited ovarian cancer. Hum Mutat 28(12):1207–1215CrossRefPubMed

38.

Gutierrez-Enriquez S, Balmana J, Baiget M, Diez O (2008) Detection of the CHEK2 1100delC mutation by MLPA BRCA1/2 analysis: a worthwhile strategy for its clinical applicability in 1100delC low-frequency populations? Breast Cancer Res Treat 107(3):455–457CrossRefPubMed

39.

Agata S, Dalla Palma M, Callegaro M et al (2005) Large genomic deletions inactivate the BRCA2 gene in breast cancer families. J Med Genet 42(10):e64CrossRefPubMed

40.

Evans DG, Lalloo F, Wallace A, Rahman N (2005) Update on the Manchester Scoring System for BRCA1 and BRCA2 testing. J Med Genet 42(7):e39CrossRefPubMed

41.

Easton DF, Deffenbaugh AM, Pruss D et al (2007) A systematic genetic assessment of 1, 433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes. Am J Hum Genet 81(5):873–883CrossRefPubMed

42.

Gagnon A, Heyer E (2001) Fragmentation of the Quebec population genetic pool (Canada): evidence from the genetic contribution of founders per region in the 17th and 18th centuries. Am J Phys Anthropol 114(1):30–41CrossRefPubMed

43.

Tonin PN, Perret C, Lambert JA et al (2001) Founder BRCA1 and BRCA2 mutations in early-onset French Canadian breast cancer cases unselected for family history. Int J Cancer 95(3):189–193CrossRefPubMed

44.

Loman N, Johannsson O, Kristoffersson U, Olsson H, Borg A (2001) Family history of breast and ovarian cancers and BRCA1 and BRCA2 mutations in a population-based series of early-onset breast cancer. J Natl Cancer Inst 93(16):1215–1223CrossRefPubMed

45.

King MC, Marks JH, Mandell JB (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302(5645):643–646CrossRefPubMed

46.

Gershoni-Baruch R, Dagan E, Fried G et al (2000) Significantly lower rates of BRCA1/BRCA2 founder mutations in Ashkenazi women with sporadic compared with familial early onset breast cancer. Eur J Cancer 36(8):983–986CrossRefPubMed

47.

Hodgson SV, Heap E, Cameron J et al (1999) Risk factors for detecting germline BRCA1 and BRCA2 founder mutations in Ashkenazi Jewish women with breast or ovarian cancer. J Med Genet 36(5):369–373PubMed

48.

Ghadirian P, Robidoux A, Zhang P et al (2009) The contribution of founder mutations to early-onset breast cancer in French-Canadian women. Clin Genet 76(5):421–426CrossRefPubMed

49.

Lee E, McKean-Cowdin R, Ma H et al (2008) Evaluation of unclassified variants in the breast cancer susceptibility genes BRCA1 and BRCA2 using five methods: results from a population-based study of young breast cancer patients. Breast Cancer Res 10(1):R19CrossRefPubMed

50.

Tal A, Arbel-Goren R, Stavans J (2009) Cancer-associated mutations in BRC domains of BRCA2 affect homologous recombination induced by Rad51. J Mol Biol 393(5):1007–1012CrossRefPubMed

Titel: Comprehensive BRCA1 and BRCA2 mutation analyses and review of French Canadian families with at least three cases of breast cancer
verfasst von: Luca Cavallone
Suzanna L. Arcand
Christine M. Maugard
Serge Nolet
Louis A. Gaboury
Anne-Marie Mes-Masson
Parviz Ghadirian
Diane Provencher
Patricia N. Tonin
Publikationsdatum: 01.12.2010
Verlag: Springer Netherlands
Erschienen in: Familial Cancer / Ausgabe 4/2010
Print ISSN: 1389-9600
Elektronische ISSN: 1573-7292
DOI: https://doi.org/10.1007/s10689-010-9372-3

Springer Medizin

Comprehensive BRCA1 and BRCA2 mutation analyses and review of French Canadian families with at least three cases of breast cancer

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2010

Contribution of CDKN2A/P16 INK4A , P14 ARF , CDK4 and BRCA1/2 germline mutations in individuals with suspected genetic predisposition to uveal melanoma

Complete BRCA mutation screening in breast and ovarian cancer predisposition families from a North-Eastern Romanian population

Disclosing cancer genetic information within families: perspectives of counselees and their at-risk relatives

BRCA1 and BRCA2 families and the risk of skin cancer

Screening for large genomic rearrangements of the BRIP1 and CHK1 genes in Finnish breast cancer families

Papillary thyroid cancer in a patient with MUTYH-associated polyposis (MAP)

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie