Lack of large genomic deletions in BRIP1, PALB2, and FANCD2 genes in BRCA1/2 negative familial breast cancer

  • Najim Ameziane
  • Ans M. W. van den Ouweland
  • Muriel A. Adank
  • Raymond N. C. P. Vijzelaar
  • Abdellatif Errami
  • Josephine C. Dorsman
  • Hans Joenje
  • Hanne Meijers-Heijboer
  • Quinten Waisfisz
Letter to the editor

To the editor

Breast cancer (BC) is the most common malignancy in women worldwide. It is estimated that 5–10% of all BC cases may be caused by germline mutations in breast cancer susceptibility genes [19, 21]. BRCA1 and BRCA2 are the major known BC susceptibility genes accounting for ~16% of the familial BC cases [2]. Other BC susceptibility genes include TP53 [16], PTEN [15], ATM [24], LKB1/STK11 [8], CHEK2 [28], BRIP1/FANCJ [27], and PALB2/FANCN [22]. However to date, the majority of familial BC cases can not be attributed to mutations in one of the known susceptibility genes.

The discovery of the breast cancer susceptibility gene BRCA2 as the gene defective in the Fanconi anemia (FA)-D1 complementation group [11], the identification of BRIP1 (BRCA1 Interacting Protein) [3, 12, 13] and PALB2 (Partner And Localizer of BRCA2) [23, 32] as the genes responsible for the FA-J and FA-N complementation groups, respectively, established a clear link between breast cancer susceptibility and...


Fanconi Anemia Large Deletion Familial Breast Cancer Breast Cancer Susceptibility Gene Fanconi Anemia Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Alter BP (2003) Cancer in Fanconi anemia, 1927–2001. Cancer 97:425–440. doi: 10.1002/cncr.11046 CrossRefPubMedGoogle Scholar
  2. 2.
    Anglian Breast Cancer Study Group (2000) Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Anglian Breast Cancer Study Group. Br J Cancer 83:1301–1308. doi: 10.1054/bjoc.2000.1407 CrossRefGoogle Scholar
  3. 3.
    Bridge WL, Vandenberg CJ, Franklin RJ et al (2005) The BRIP1 helicase functions independently of BRCA1 in the Fanconi anemia pathway for DNA crosslink repair. Nat Genet 37:953–957. doi: 10.1038/ng1627 CrossRefPubMedGoogle Scholar
  4. 4.
    Cao AY, Huang J, Hu Z et al (2009) The prevalence of PALB2 germline mutations in BRCA1/BRCA2 negative Chinese women with early onset breast cancer or affected relatives. Breast Cancer Res Treat 114:457–462. doi: 10.1007/s10549-008-0036-z CrossRefPubMedGoogle Scholar
  5. 5.
    Erkko H, Xia B, Nikkila J et al (2007) A recurrent mutation in PALB2 in Finnish cancer families. Nature 446:316–319. doi: 10.1038/nature05609 CrossRefPubMedGoogle Scholar
  6. 6.
    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:R83. doi: 10.1186/bcr1828 CrossRefPubMedGoogle Scholar
  7. 7.
    Garcia MJ, Fernandez V, Osorio A et al (2008) Analysis of FANCB and FANCN/PALB2 Fanconi anemia genes in BRCA1/2-negative Spanish breast cancer families. Breast Cancer Res Treat 113:545–551. doi: 10.1007/s10549-008-9945-0 CrossRefPubMedGoogle Scholar
  8. 8.
    Giardiello FM, Brensinger JD, Tersmette AC et al (2000) Very high risk of cancer in familial Peutz–Jeghers syndrome. Gastroenterology 119:1447–1453. doi: 10.1053/gast.2000.20228 CrossRefPubMedGoogle Scholar
  9. 9.
    Gunnarsson H, Arason A, Gillanders EM et al (2008) Evidence against PALB2 involvement in Icelandic breast cancer susceptibility. J Negat Results Biomed 7:5. doi: 10.1186/1477-5751-7-5 CrossRefPubMedGoogle Scholar
  10. 10.
    Houghtaling S, Timmers C, Noll M et al (2003) Epithelial cancer in Fanconi anemia complementation group D2 (Fancd2) knockout mice. Genes Dev 17:2021–2035. doi: 10.1101/gad.1103403 CrossRefPubMedGoogle Scholar
  11. 11.
    Howlett NG, Taniguchi T, Olson S et al (2002) Biallelic inactivation of BRCA2 in Fanconi anemia. Science 297:606–609. doi: 10.1126/science.1073834 CrossRefPubMedGoogle Scholar
  12. 12.
    Levitus M, Waisfisz Q, Godthelp BC et al (2005) The DNA helicase BRIP1 is defective in Fanconi anemia complementation group J. Nat Genet 37:934–935. doi: 10.1038/ng1625 CrossRefPubMedGoogle Scholar
  13. 13.
    Levran O, Attwooll C, Henry RT et al (2005) The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia. Nat Genet 37:931–933. doi: 10.1038/ng1624 CrossRefPubMedGoogle Scholar
  14. 14.
    Lewis AG, Flanagan J, Marsh A et al (2005) Mutation analysis of FANCD2, BRIP1/BACH1, LMO4 and SFN in familial breast cancer. Breast Cancer Res 7:R1005–R1016. doi: 10.1186/bcr1336 CrossRefPubMedGoogle Scholar
  15. 15.
    Lynch ED, Ostermeyer EA, Lee MK et al (1997) Inherited mutations in PTEN that are associated with breast cancer, cowden disease, and juvenile polyposis. Am J Hum Genet 61:1254–1260. doi: 10.1086/301639 CrossRefPubMedGoogle Scholar
  16. 16.
    Malkin D, Li FP, Strong LC et al (1990) Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250:1233–1238. doi: 10.1126/science.1978757 CrossRefPubMedGoogle Scholar
  17. 17.
    Mathew CG (2006) Fanconi anaemia genes and susceptibility to cancer. Oncogene 25:5875–5884. doi: 10.1038/sj.onc.1209878 CrossRefPubMedGoogle Scholar
  18. 18.
    Meijer GA (2007) The 13th Fanconi anemia gene identified: FANCI—importance of the ‘Fanconi anemia pathway’ for cellular oncology. Cell Oncol 29:181–182PubMedGoogle Scholar
  19. 19.
    Oldenburg RA, Meijers-Heijboer H, Cornelisse CJ et al (2007) Genetic susceptibility for breast cancer: how many more genes to be found? Crit Rev Oncol Hematol 63:125–149. doi: 10.1016/j.critrevonc.2006.12.004 CrossRefPubMedGoogle Scholar
  20. 20.
    Pylkas K, Erkko H, Nikkila J et al (2008) Analysis of large deletions in BRCA1, BRCA2 and PALB2 genes in Finnish breast and ovarian cancer families. BMC Cancer 8:146. doi: 10.1186/1471-2407-8-146 CrossRefPubMedGoogle Scholar
  21. 21.
    Rahman N, Scott RH (2007) Cancer genes associated with phenotypes in monoallelic and biallelic mutation carriers: new lessons from old players. Hum Mol Genet 16:60–66 Spec No 1:CrossRefGoogle Scholar
  22. 22.
    Rahman N, Seal S, Thompson D et al (2007) PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet 39:165–167. doi: 10.1038/ng1959 CrossRefPubMedGoogle Scholar
  23. 23.
    Reid S, Schindler D, Hanenberg H et al (2007) Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nat Genet 39:162–164. doi: 10.1038/ng1947 CrossRefPubMedGoogle Scholar
  24. 24.
    Renwick AD, Thompson S, Seal P et al (2006) ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat Genet 38:873–875. doi: 10.1038/ng1837 CrossRefPubMedGoogle Scholar
  25. 25.
    Schouten JP, McElgunn CJ, Waaijer R et al (2002) Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 30:e57. doi: 10.1093/nar/gnf056 CrossRefPubMedGoogle Scholar
  26. 26.
    Seal S, Barfoot R, Jayatilake H et al (2003) Evaluation of Fanconi anemia genes in familial breast cancer predisposition. Cancer Res 63:8596–8599PubMedGoogle Scholar
  27. 27.
    Seal S, Thompson D, Renwick A et al (2006) Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nat Genet 38:1239–1241. doi: 10.1038/ng1902 CrossRefPubMedGoogle Scholar
  28. 28.
    The CHEK2 Breast Cancer Case-Control Consortium (2004) CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10, 860 breast cancer cases and 9, 065 controls from 10 studies. Am J Hum Genet 74:1175–1182. doi: 10.1086/421251 CrossRefGoogle Scholar
  29. 29.
    Tischkowitz M, Sabbaghian N, Ray AM et al (2008) Analysis of the gene coding for the BRCA2-interacting protein PALB2 in hereditary prostate cancer. Prostate 68:675–678. doi: 10.1002/pros.20729 CrossRefPubMedGoogle Scholar
  30. 30.
    Van der Hout AH, van den Ouweland AM, van der Luijt RB et al (2006) A DGGE system for comprehensive mutation screening of BRCA1 and BRCA2: application in a Dutch cancer clinic setting. Hum Mutat 27:654–666. doi: 10.1002/humu.20340 CrossRefPubMedGoogle Scholar
  31. 31.
    Wang W (2007) Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins. Nat Rev Genet 8:735–748. doi: 10.1038/nrg2159 CrossRefPubMedGoogle Scholar
  32. 32.
    Xia B, Dorsman JC, Ameziane N et al (2007) Fanconi anemia is associated with a defect in the BRCA2 partner PALB2. Nat Genet 39:159–161. doi: 10.1038/ng1942 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Najim Ameziane
    • 1
  • Ans M. W. van den Ouweland
    • 2
  • Muriel A. Adank
    • 1
  • Raymond N. C. P. Vijzelaar
    • 3
  • Abdellatif Errami
    • 3
  • Josephine C. Dorsman
    • 1
  • Hans Joenje
    • 1
  • Hanne Meijers-Heijboer
    • 1
  • Quinten Waisfisz
    • 1
  1. 1.Department of Clinical Genetics, Section OncogeneticsVU University Medical CenterAmsterdamThe Netherlands
  2. 2.Department of Clinical GeneticsErasmus Medical CenterRotterdamThe Netherlands
  3. 3.MRC-HollandAmsterdamThe Netherlands

Personalised recommendations