
MOLECULAR GENETICS OF BREAST AND OVARIAN
CANCER: RECENT ADVANCES AND CLINICAL IMPLICATIONS Bogdanova N1,2, Dörk T2,* *Corresponding Author: Thilo Dörk, Ph.D., Hannover Medical School, Gynaecology Research Unit (OE
6411), Carl-Neuberg-Str. 1, D-30625 Hannover, Germany; Tel.: +49-511-532-6075; Fax: +49-511-532-
6081; E-mail: doerk.thilo@mh-hannover.de page: 75
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REFERENCES
1. Turnbull C, Rahman N. Genetic predisposition to
breast cancer: past, present, and future. Annu Rev
Genomics Hum Genet. 2008; 9: 321-345.
2. Ghoussaini M, Pharoah PD. Polygenic susceptibility
to breast cancer: current state-of-the-art. Future
Oncol. 2009; 5(5): 689-701.
3. Gayther SA, Pharoah PD. The inherited genetics of
ovarian and endometrial cancer. Curr Opin Genet
Dev. 2010; 20(3): 231-238.
4. Risch HA, McLaughlin JR, Cole DE, et al. Prevalence
and penetrance of germline BRCA1 and BRCA2
mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet. 2001; 68(3): 700-
710.
5. Thompson D, Easton D, Breast Cancer Linkage
Consortium. Variation in cancer risks, by mutation
position, in BRCA2 mutation carriers. Am J Hum
Genet. 2001; 68(2): 410-419.
6. Bogdanova NV, Antonenkova NN, Rogov YI,
Karstens JH, Hillemanns P, Dörk T. High frequency
and allele-specific differences of BRCA1 founder
mutations in breast cancer and ovarian cancer patients
from Belarus. Clin Genet. 2010; 78(4): 364-372.
7. Antoniou AC, Sinilnikova OM, Simard J, et al.
RAD51 135G>C modifies breast cancer risk among
BRCA2 mutation carriers: results from a combined
analysis of 19 studies. Am J Hum Genet. 2007;
81(6): 1186-1200.
8. Ramus SJ, Kartsonaki C, Gayther SA, Pharoah
PD, Sinilnikova OM, Beesley J. Genetic variation
at 9p22.2 and ovarian cancer risk for BRCA1 and
BRCA2 mutation carriers. J Natl Cancer Inst. 2011;
103(2): 105-116.
9. Rahman N, Seal S, Thompson D, et al. PALB2,
which encodes a BRCA2-interacting protein, is a
breast cancer susceptibility gene. Nat Genet. 2007;
39(2): 165-167.
10. Erkko H, Xia B, Nikkilä J, et al. A recurrent mutation
in PALB2 in Finnish cancer families. Nature. 2007;
446(7133): 316-319.
11. Erkko H, Dowty JG, Nikkilä J, et al. Penetrance
analysis of the PALB2 c.1592delT founder mutation.
Clin Cancer Res 2008;14(14):4667-4671.
12. Dansonka-Mieszkowska A, Kluska A, Moes J, et al.
A novel germline PALB2 deletion in Polish breast
and ovarian cancer patients. BMC Med Genet. 2010;
11: 20.
13. Prokofyeva D, Bogdanova N, Bermisheva M, et al.
Rare occurrence of PALB2 mutations in ovarian
cancer patients from the Volga-Ural region. Clin
Genet. 2012; 82(1): 100-101.
14. Meindl A, Hellebrand H, Wiek C, et al. Germline
mutations in breast and ovarian cancer pedigrees
establish RAD51C as a human cancer susceptibility
gene. Nat Genet. 2010; 42(5): 410-414.
15. Pelttari LM, Heikkinen T, Thompson D, et al.
RAD51C is a susceptibility gene for ovarian cancer.
Hum Mol Genet. 2011; 20(16): 3278-3288.
16. Loveday C, Turnbull C, Ramsay E, Hughes D, Ruark
E, Frankum JR. Germline mutations in RAD51D
confer susceptibility to ovarian cancer. Nat Genet.
2011; 43(9): 879-882.
17. Seal S, Thompson D, Renwick A, et al. Truncating
mutations in the Fanconi anemia J gene BRIP1 are
low-penetrance breast cancer susceptibility alleles.
Nat Genet. 2006; 38(11): 1239-1241. 18. Masciari S, Larsson N, Senz J, et al. Germline
E-cadherin mutations in familial lobular breast
cancer. J Med Genet. 2007; 44(11): 726-731.
19. Xie ZM, Li LS, Laquet C, et al. Germline mutations
of the E-cadherin gene in families with inherited
invasive lobular breast carcinoma but no diffuse
gastric cancer. Cancer. 2011; 117(14): 3112-3117.
20. Swift M, Reitnauer PJ, Morrell D, Chase CL.
Breast and other cancers in families with ataxiatelangiectasia.
N Engl J Med. 1987; 316(21): 1289-
1294.
21. Shiloh Y. ATM and related protein kinases:
safeguarding genome integrity. Nat Rev Cancer.
2003; 3(3): 155-168.
22. Renwick A, Thompson D, Seal S, et al. ATM
mutations that cause ataxia-telangiectasia are breast
cancer susceptibility alleles. Nat Genet. 2006; 38(8):
873-875.
23. Pylkäs K, Tommiska J, Syrjäkoski K, et al. Evaluation
of the role of Finnish ataxia-telangiectasia mutations
in hereditary predisposition to breast cancer.
Carcinogenesis. 2007; 28(5): 1040-1045.
24. Bogdanova N, Cybulski C, Bermisheva M, et al.
A nonsense mutation (E1978X) in the ATM gene
is associated with breast cancer. Breast Cancer Res
Treat. 2009; 118(1): 207-211.
25. Górski B, Cybulski C, Huzarski T, et al. Breast
cancer predisposing alleles in Poland. Breast Cancer
Res Treat. 2005; 92(1): 19-24.
26. Steffen J, Nowakowska D, Niwinska A, et al.
Germline mutations 657del5 of the NBS1 gene
contribute significantly to the incidence of breast
cancer in Central Poland. Int J Cancer. 2006; 119(2):
472-475.
27. Bogdanova N, Feshchenko S, Schürmann P, et al.
Nijmegen Breakage Syndrome mutations and risk of
breast cancer. Int J Cancer. 2008; 122(4): 802-806.
28. Heikkinen K, Rapakko K, Karppinen SM, et al.
RAD50 and NBS1 are breast cancer susceptibility
genes associated with genomic instability.
Carcinogenesis. 2006; 27(8): 1593-1599.
29. Bartkova J, Tommiska J, Oplustilova L, et al.
Aberrations of the MRE11-RAD50-NBS1 DNA
damage sensor complex in human breast cancer:
MRE11 as a candidate familial cancer-predisposing
gene. Mol Oncol. 2008; 2(4): 296-316.
30. Walsh T, Casadei S, Lee MK, et al. Mutations in
12 genes for inherited ovarian, fallopian tube, and
peritoneal carcinoma identified by massively parallel
sequencing. Proc Natl Acad Sci USA. 2011; 108(44):
18032-18037.
31. Nevanlinna H, Bartek J. The CHEK2 gene and
inherited breast cancer susceptibility. Oncogene.
2006; 25(43): 5912-5919. 32. Meijers-Heijboer H, van den Ouweland A, Klijn
J, et al; CHEK2-Breast Cancer Consortium. Lowpenetrance
susceptibility to breast cancer due to
CHEK2(*)1100delC in noncarriers of BRCA1 or
BRCA2 mutations. Nat Genet. 2002; 31(1): 55-59.
33. Vahteristo P, Bartkova J, Eerola H, et al. A CHEK2
genetic variant contributing to a substantial fraction
of familial breast cancer. Am J Hum Genet. 2002;
71(2): 432-438.
34. CHEK2 Breast Cancer Case-Control Consortium.
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. 2004; 74(6): 1175-1182.
35. Adank MA, Jonker MA, Kluijt I, et al. CHEK2*
1100delC homozygosity is associated with a high
breast cancer risk in women. J Med Genet. 2011;
48(12): 860-863.
36. Cybulski C, Wokołorczyk D, Huzarski T, et al. A
deletion in CHEK2 of 5,395 bp predisposes to breast
cancer in Poland. Breast Cancer Res Treat. 2007;
102(1): 119-122.
37. Bogdanova N, Enssen-Dubrowinskaja N,
Feshchenko S, et al. Association of two mutations
in the CHEK2 gene with breast cancer. Int J Cancer.
2005; 116(2): 263-266.
38. Cybulski C, Górski B, Huzarski T, et al. CHEK2 is
a multiorgan cancer susceptibility gene. Am J Hum
Genet. 2004; 75(6): 1131-1135.
39. Easton DF, Pooley KA, Dunning AM, et al. Genomewide
association study identifies novel breast cancer
susceptibility loci. Nature. 2007; 447(7148): 1087-1093.
40. Ahmed S, Thomas G, Ghoussaini M, et al. Newly
discovered breast cancer susceptibility loci on 3p24
and 17q23.2. Nat Genet. 2009; 41(5): 585-590.
41. Antoniou AC, Wang X, Fredericksen ZS, et al. A
locus on 19p13 modifies risk of breast cancer in
BRCA1 mutation carriers and is associated with
hormone receptor-negative breast cancer in the
general population. Nat Genet 2010;42(10):885-892.
42. Turnbull C, Ahmed S, Morrison J, et al. Genomewide
association study identifies five new breast
cancer susceptibility loci. Nat Genet. 2010; 42(6):
504-507.
43. Haiman CA, Chen GK, Vachon CM, et al. A common
variant at the TERT-CLPTM1L locus is associated
with estrogen receptor-negative breast cancer. Nat
Genet. 2011; 43(12): 1210-1214.
44. Long J, Cai Q, Sung H, et al. Genome-wide
association study in East Asians identifies novel
susceptibility loci for breast cancer. PLoS Genet.
2012; 8(2): e1002532.
45. Ghoussaini M, Fletcher O, Michailidou K, et al.
Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nat Genet.
2012; 44(3): 312-318.
46. Song H, Ramus SJ, Tyrer J, et al. A genome-wide
association study identifies a new ovarian cancer
susceptibility locus on 9p22.2. Nat Genet. 2009;
41(9): 996-1000.
47. Goode EL, Chenevix-Trench G, Song H, et al.
A genome-wide association study identifies
susceptibility loci for ovarian cancer at 2q31 and
8q24. Nat Genet. 2010; 42(10): 874-879.
48. Bolton KL, Tyrer J, Song H, et al. Common variants
at 19p13 are associated with susceptibility to ovarian
cancer. Nat Genet. 2010; 42(10): 880-884.
49. Ghoussaini M, Song H, Koessler T, et al. Multiple
loci with different cancer specificities within the
8q24 gene desert. J Natl Cancer Inst. 2008; 100(13):
962-966.
50. Wellcome Trust Case Control Consortium. Genomewide
association study of CNVs in 16,000 cases of
eight common diseases and 3,000 shared controls.
Nature. 2010; 464(7289): 713-720.
51. Pharoah PD, Antoniou AC, Easton DF, Ponder BA.
Polygenes, risk prediction, and targeted prevention
of breast cancer. N Engl J Med. 2008; 358(26): 2796-
2803.
52. Pashayan N, Duffy SW, Chowdhury S, et al.
Polygenic susceptibility to prostate and breast
cancer: implications for personalised screening. Br J
Cancer. 2011; 104 (10): 1656-1663. 53. Robertson L, Hanson H, Seal S, et al. BRCA1 testing
should be offered to individuals with triple-negative
breast cancer diagnosed below 50 years. Br J Cancer.
2012; 106(6): 1234-1238.
54. Broeks A, Schmidt MK, Sherman ME, et al. Low
penetrance breast cancer susceptibility loci are
associated with specific breast tumor subtypes:
findings from the Breast Cancer Association
Consortium. Hum Mol Genet. 2011; 20(16): 3289-
3303.
55. Hynes NE, Dey JH. Potential for targeting the
fibroblast growth factor receptors in breast cancer.
Cancer Res. 2010; 70(13): 5199-5202.
56. Bolton KL, Chenevix-Trench G, Goh C, et al.
Association between BRCA1 and BRCA2 mutations
and survival in women with invasive epithelial
ovarian cancer. JAMA. 2012; 307(4): 382-390.
57. Dedes KJ, Wilkerson PM, Wetterskog D, Weigelt
B, Ashworth A, Reis-Filho JS. Synthetic lethality
of PARP inhibition in cancers lacking BRCA1 and
BRCA2 mutations. Cell Cycle. 2011; 10(8): 1192-
1199.
58. Reaper PM, Griffiths MR, Long JM, et al. Selective
killing of ATM- or p53-deficient cancer cells through
inhibition of ATR. Nat Chem Biol. 2011; 7(7): 428-
430.
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