Family-specific, novel, deleterious germline variants provide a rich resource to identify genetic predispositions for BRCAx familial breast cancer
详细信息 查看全文
- 作者：Hongxiu Wen (5)
Yeong C Kim (5)
Carrie Snyder (6)
Fengxia Xiao (5)
Elizabeth A Fleissner (7)
Dina Becirovic (6)
Jiangtao Luo (8)
Bradley Downs (5)
Simon Sherman (7)
Kenneth H Cowan (7)
Henry T Lynch (5) (6) (9)
San Ming Wang (5) (7)
5. Department of Genetics ; Cell Biology and Anatomy ; College of Medicine ; University of Nebraska Medical Center ; 986805 Nebraska Medical Center ; Omaha ; NE ; 68198 ; USA
6. Hereditary Cancer Center ; Department of Preventive Medicine ; Creighton University School of Medicine ; 2500 California Plaza ; Omaha ; NE ; 68178 ; USA
7. Fred & Pamela Buffett Cancer Center ; Omaha ; USA
8. Department of Biostatistics ; College of Public Health ; University of Nebraska Medical Center ; Omaha ; USA
9. Department of Medicine ; Creighton University School of Medicine ; 2500 California Plaza ; Omaha ; NE ; 68178 ; USA - 刊名：BMC Cancer
- 出版年：2014
- 出版时间：December 2014
- 年：2014
- 卷：14
- 期：1
- 全文大小：3,174 KB
- 参考文献：Cancer Facts & Figures 鈥?2013.
1. Rahman, N, Stratton, MR (1998) The genetics of breast cancer susceptibility. Annu Rev Genet 32: pp. 95-121 ss="external" href="http://dx.doi.org/10.1146/annurev.genet.32.1.95" target="_blank" title="It opens in new window">CrossRef
2. Stratton, MR, Rahman, N (2008) The emerging landscape of breast cancer susceptibility. Nat Genet 40: pp. 17-22 ss="external" href="http://dx.doi.org/10.1038/ng.2007.53" target="_blank" title="It opens in new window">CrossRef
3. Stephens, PJ, Tarpey, PS, Davies, H, Van Loo, P, Greenman, C, Wedge, DC, Nik-Zainal, S, Martin, S, Varela, I, Bignell, GR, Yates, LR, Papaemmanuil, E, Beare, D, Butler, A, Cheverton, A, Gamble, J, Hinton, J, Jia, M, Jayakumar, A, Jones, D, Latimer, C, Lau, KW, McLaren, S, McBride, DJ, Menzies, A, Mudie, L, Raine, K, Rad, R, Chapman, MS, Teague, J (2012) The landscape of cancer genes and mutational processes in breast cancer. Nature 486: pp. 400-404
4. Park, DJ, Lesueur, F, Nguyen-Dumont, T, Pertesi, M, Odefrey, F, Hammet, F, Neuhausen, SL, John, EM, Andrulis, IL, Terry, MB, Daly, M, Buys, S, Le Calvez-Kelm, F, Lonie, A, Pope, BJ, Tsimiklis, H, Voegele, C, Hilbers, FM, Hoogerbrugge, N, Barroso, A, Osorio, A, Giles, GG, Devilee, P, Benitez, J, Hopper, JL, Tavtigian, SV, Goldgar, DE, Southey, MC (2012) Rare mutations in XRCC2 increase the risk of breast cancer. Am J Hum Genet 90: pp. 734-739 ss="external" href="http://dx.doi.org/10.1016/j.ajhg.2012.02.027" target="_blank" title="It opens in new window">CrossRef
5. Thompson, ER, Doyle, MA, Ryland, GL, Rowley, SM, Choong, DY, Tothill, RW, Thorne, H, Barnes, DR, Li, J, Ellul, J, Philip, GK, Antill, YC, James, PA, Trainer, AH, Mitchell, G, Campbell, IG (2012) Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles. PLoS Genet 8: pp. e1002894 ss="external" href="http://dx.doi.org/10.1371/journal.pgen.1002894" target="_blank" title="It opens in new window">CrossRef
6. Snape, K, Ruark, E, Tarpey, P, Renwick, A, Turnbull, C, Seal, S, Murray, A, Hanks, S, Douglas, J, Stratton, MR, Rahman, N (2012) Predisposition gene identification in common cancers by exome sequencing: insights from familial breast cancer. Breast Cancer Res Treat 134: pp. 429-433 ss="external" href="http://dx.doi.org/10.1007/s10549-012-2057-x" target="_blank" title="It opens in new window">CrossRef
7. Gracia-Aznarez, FJ, Fernandez, V, Pita, G, Peterlongo, P, Dominguez, O, de la Hoya, M, Duran, M, Osorio, A, Moreno, L, Gonzalez-Neira, A, Rosa-Rosa, JM, Sinilnikova, O, Mazoyer, S, Hopper, J, Lazaro, C, Southey, M, Odefrey, F, Manoukian, S, Catucci, I, Caldes, T, Lynch, HT, Hilbers, FS, van Asperen, CJ, Vasen, HF, Goldgar, D, Radice, P, Devilee, P, Benitez, J (2013) Whole exome sequencing suggests much of non-BRCA1/BRCA2 familial breast cancer is due to moderate and low penetrance susceptibility alleles. PLoS One 8: pp. e55681 ss="external" href="http://dx.doi.org/10.1371/journal.pone.0055681" target="_blank" title="It opens in new window">CrossRef
8. Hilbers, FS, Meijers, CM, Laros, JF, van Galen, M, Hoogerbrugge, N, Vasen, HF, Nederlof, PM, Wijnen, JT, van Asperen, CJ, Devilee, P (2013) Exome sequencing of germline DNA from non-BRCA1/2 familial breast cancer cases selected on the basis of aCGH tumor profiling. PLoS One 8: pp. e55734 ss="external" href="http://dx.doi.org/10.1371/journal.pone.0055734" target="_blank" title="It opens in new window">CrossRef
9. Hilbers, FS, Meijers, CM, Laros, JF, van Galen, M, Hoogerbrugge, N, Vasen, HF, Nederlof, PM, Wijnen, JT, van Asperen, CJ, Devilee, P (2012) Rare variants in XRCC2 as breast cancer susceptibility alleles. J Med Genet 49: pp. 618-620 ss="external" href="http://dx.doi.org/10.1136/jmedgenet-2012-101191" target="_blank" title="It opens in new window">CrossRef
10. Ruark, E, Snape, K, Humburg, P, Loveday, C, Bajrami, I, Brough, R, Rodrigues, DN, Renwick, A, Seal, S, Ramsay, E, Duarte Sdel, V, Rivas, MA, Warren-Perry, M, Zachariou, A, Campion-Flora, A, Hanks, S, Murray, A, Ansari Pour, N, Douglas, J, Gregory, L, Rimmer, A, Walker, NM, Yang, TP, Adlard, JW, Barwell, J, Berg, J, Brady, AF, Brewer, C, Brice, G, Chapman, C (2013) Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer. Nature 493: pp. 406-410 ss="external" href="http://dx.doi.org/10.1038/nature11725" target="_blank" title="It opens in new window">CrossRef
11. Lynch, HT, Krush, AJ, Lemon, HM, Kaplan, AR, Condit, PT, Bottomley, RH (1972) Tumor variation in families with breast cancer. JAMA 222: pp. 1631-1635 ss="external" href="http://dx.doi.org/10.1001/jama.1972.03210130023005" target="_blank" title="It opens in new window">CrossRef
12. Lynch, H, Wen, H, Kim, YC, Snyder, C, Kinarsky, Y, Chen, PX, Xiao, F, Goldgar, D, Cowan, KH, Wang, SM (2013) Can unknown predisposition in familial breast cancer be family-specific?. Breast J 19: pp. 520-528
13. Langmead, B, Salzberg, SL (2012) Fast gapped-read alignment with Bowtie2. Nat Methods 9: pp. 357-359 ss="external" href="http://dx.doi.org/10.1038/nmeth.1923" target="_blank" title="It opens in new window">CrossRef
14. McKenna, A, Hanna, M, Banks, E, Sivachenko, A, Cibulskis, K, Kernytsky, A, Garimella, K, Altshuler, D, Gabriel, S, Daly, M, DePristo, MA (2010) The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20: pp. 1297-1303 ss="external" href="http://dx.doi.org/10.1101/gr.107524.110" target="_blank" title="It opens in new window">CrossRef
15. Koboldt, DC, Zhang, Q, Larson, DE, Shen, D, McLellan, MD, Lin, L, Miller, CA, Mardis, ER, Ding, L, Wilson, RK (2012) VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res 22: pp. 568-576 ss="external" href="http://dx.doi.org/10.1101/gr.129684.111" target="_blank" title="It opens in new window">CrossRef
16. Li, H, Handsaker, B, Wysoker, A, Fennell, T, Ruan, J, Homer, N, Marth, G, Abecasis, G, Durbin, R (2009) 1000 Genome Project Data Processing Subgroup, 1000 Genome Project Data. The sequence alignment/map (SAM) format and SAMtools. Bioinformatics 25: pp. 2078-2079 ss="external" href="http://dx.doi.org/10.1093/bioinformatics/btp352" target="_blank" title="It opens in new window">CrossRef
17. Adzhubei, IA, Schmidt, S, Peshkin, L, Ramensky, VE, Gerasimova, A, Bork, P, Kondrashov, AS, Sunyaev, SR (2010) A method and server for predicting damaging missense mutations. Nat Methods 7: pp. 248-249 ss="external" href="http://dx.doi.org/10.1038/nmeth0410-248" target="_blank" title="It opens in new window">CrossRef
18. Lonita-Laza, I, Ottman, R (2011) Study designs for identification of rare disease variants in complex diseases: the utility of family-based designs. Genetics 189: pp. 1061-1068 ss="external" href="http://dx.doi.org/10.1534/genetics.111.131813" target="_blank" title="It opens in new window">CrossRef
19. Machin, D, Campbell, M, Fayers, P, Pinol, A (1997) Sample Size Tables for Clinical Studies. Blackwell Science, Malden, MA
20. Bamshad, MJ, Ng, SB, Bigham, AW, Tabor, HK, Emond, MJ, Nickerson, DA, Shendure, J (2011) Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet 12: pp. 745-755 ss="external" href="http://dx.doi.org/10.1038/nrg3031" target="_blank" title="It opens in new window">CrossRef
21. Valente, EM, Abou-Sleiman, PM, Caputo, V, Muqit, MM, Harvey, K, Gispert, S, Ali, Z, Del Turco, D, Bentivoglio, AR, Healy, DG, Albanese, A, Nussbaum, R, Gonz谩lez-Maldonado, R, Deller, T, Salvi, S, Cortelli, P, Gilks, WP, Latchman, DS, Harvey, RJ, Dallapiccola, B, Auburger, G, Wood, NW (2004) Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 304: pp. 1158-1160 ss="external" href="http://dx.doi.org/10.1126/science.1096284" target="_blank" title="It opens in new window">CrossRef
22. Champagne, N, Bertos, NR, Pelletier, N, Wang, AH, Vezmar, M, Yang, Y, Heng, HH, Yang, XJ (1999) Identification of a human histone acetyltransferase related to monocytic leukemia zinc finger protein. J Biol Chem 274: pp. 28528-28536 ss="external" href="http://dx.doi.org/10.1074/jbc.274.40.28528" target="_blank" title="It opens in new window">CrossRef
23. Kraft, M, Cirstea, IC, Voss, AK, Thomas, T, Goehring, I, Sheikh, BN, Gordon, L, Scott, H, Smyth, GK, Ahmadian, MR, Trautmann, U, Zenker, M, Tartaglia, M, Ekici, A, Reis, A, D枚rr, HG, Rauch, A, Thiel, CT (2011) Disruption of the histone acetyltransferase MYST4 leads to a Noonan syndrome-like phenotype and hyperactivated MAPK signaling in humans and mice. J Clin Invest 121: pp. 3479-3491 ss="external" href="http://dx.doi.org/10.1172/JCI43428" target="_blank" title="It opens in new window">CrossRef
24. Mazzone, M, Selfors, LM, Albeck, J, Overholtzer, M, Sale, S, Carroll, DL, Pandya, D, Lu, Y, Mills, GB, Aster, JC, Artavanis-Tsakonas, S, Brugge, JS (2010) Dose-dependent induction of distinct phenotypic responses to Notch pathway activation in mammary epithelial cells. Proc Natl Acad Sci U S A 107: pp. 5012-5017 ss="external" href="http://dx.doi.org/10.1073/pnas.1000896107" target="_blank" title="It opens in new window">CrossRef
25. Simpson, MA, Irving, MD, Asilmaz, E, Gray, MJ, Dafou, D, Elmslie, FV, Mansour, S, Holder, SE, Brain, CE, Burton, BK, Kim, KH, Pauli, RM, Aftimos, S, Stewart, H, Kim, CA, Holder-Espinasse, M, Robertson, SP, Drake, WM, Trembath, RC (2011) Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. Nat Genet 43: pp. 303-305 ss="external" href="http://dx.doi.org/10.1038/ng.779" target="_blank" title="It opens in new window">CrossRef
26. Douglas, P, Zhong, J, Ye, R, Moorhead, GB, Xu, X, Lees-Miller, SP (2010) Protein phosphatase 6 interacts with the DNA-dependent protein kinase catalytic subunit and dephosphorylates gamma-H2AX. Mol Cell Biol 30: pp. 1368-1381 ss="external" href="http://dx.doi.org/10.1128/MCB.00741-09" target="_blank" title="It opens in new window">CrossRef
27. van den Berg, IE, van Beurden, EA, de Klerk, JB, van Diggelen, OP, Malingr茅, HE, Boer, MM, Berger, R (1997) Autosomal recessive phosphorylase kinase deficiency in liver, caused by mutations in the gene encoding the beta subunit (PHKB). Am J Hum Genet 61: pp. 539-546 ss="external" href="http://dx.doi.org/10.1086/515502" target="_blank" title="It opens in new window">CrossRef
28. Lone, S, Townson, SA, Uljon, SN, Johnson, RE, Brahma, A, Nair, DT, Prakash, S, Prakash, L, Aggarwal, AK (2007) Human DNA polymerase kappa encircles DNA: implications for mismatch extension and lesion bypass. Mol Cell 25: pp. 601-614 ss="external" href="http://dx.doi.org/10.1016/j.molcel.2007.01.018" target="_blank" title="It opens in new window">CrossRef
29. Seki, M, Masutani, C, Yang, LW, Schuffert, A, Iwai, S, Bahar, I, Wood, RD (2005) High-efficiency bypass of DNA damage by human DNA polymerase Q. EMBO J 23: pp. 4484-4494 ss="external" href="http://dx.doi.org/10.1038/sj.emboj.7600424" target="_blank" title="It opens in new window">CrossRef
30. van der Spek, PJ, Smit, EM, Beverloo, HB, Sugasawa, K, Masutani, C, Hanaoka, F, Hoeijmakers, JH, Hagemeijer, A (1995) Chromosomal localization of three repair genes: the xeroderma pigmentosum group C gene and two human homologs of yeast RAD23. Genomics 23: pp. 651-658 ss="external" href="http://dx.doi.org/10.1006/geno.1994.1554" target="_blank" title="It opens in new window">CrossRef
31. Ellenberger, T, Tomkinson, AE (2008) Eukaryotic DNA ligases: structural and functional insights. Annu Rev Biochem 77: pp. 313-338 ss="external" href="http://dx.doi.org/10.1146/annurev.biochem.77.061306.123941" target="_blank" title="It opens in new window">CrossRef
32. O'Driscoll, M, Cerosaletti, KM, Girard, PM, Dai, Y, Stumm, M, Kysela, B, Hirsch, B, Gennery, A, Palmer, SE, Seidel, J, Gatti, RA, Varon, R, Oettinger, MA, Neitzel, H, Jeggo, PA, Concannon, P (2001) DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol Cell 8: pp. 1175-1185 ss="external" href="http://dx.doi.org/10.1016/S1097-2765(01)00408-7" target="_blank" title="It opens in new window">CrossRef
33. Kouros-Mehr, H, Slorach, EM, Sternlicht, MD, Werb, Z (2006) GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland. Cell 127: pp. 1041-1055 ss="external" href="http://dx.doi.org/10.1016/j.cell.2006.09.048" target="_blank" title="It opens in new window">CrossRef
34. Kouros-Mehr, H, Kim, JW, Bechis, SK, Werb, Z (2008) GATA-3 and the regulation of the mammary luminal cell fate. Curr Opin Cell Biol 20: pp. 164-170 ss="external" href="http://dx.doi.org/10.1016/j.ceb.2008.02.003" target="_blank" title="It opens in new window">CrossRef
35. Network, CGA (2012) Comprehensive molecular portraits of human breast tumours. Nature 490: pp. 61-70 ss="external" href="http://dx.doi.org/10.1038/nature11453" target="_blank" title="It opens in new window">CrossRef
36. Wilson, BJ, Giguere, V (2008) Meta-analysis of human cancer microarrays reveals that GATA3 is integral to the estrogen receptor alpha pathway. Mol Cancer 7: pp. 49 ss="external" href="http://dx.doi.org/10.1186/1476-4598-7-49" target="_blank" title="It opens in new window">CrossRef
37. Dydensborg, AB, Rose, AA, Wilson, BJ, Grote, D, Paquet, M, Gigu猫re, V, Siegel, PM, Bouchard, M (2009) GATA3 inhibits breast cancer growth and pulmonary breast cancer metastasis. Oncogene 28: pp. 2634-2642 ss="external" href="http://dx.doi.org/10.1038/onc.2009.126" target="_blank" title="It opens in new window">CrossRef
38. Rowley, JD (1973) A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243: pp. 290-293 ss="external" href="http://dx.doi.org/10.1038/243290a0" target="_blank" title="It opens in new window">CrossRef
39. Southey, MC, Park, DJ, Nguyen-Dumont, T, Campbell, I, Thompson, E, Trainer, AH, Chenevix-Trench, G, Simard, J, Dumont, M, Soucy, P, Thomassen, M, J酶nson, L, Pedersen, IS, Hansen, TV, Nevanlinna, H, Khan, S, Sinilnikova, O, Mazoyer, S, Lesueur, F, Damiola, F, Schmutzler, R, Meindl, A, Hahnen, E, Dufault, MR, Chris Chan, T, Kwong, A, Barkard贸ttir, R, Radice, P, Peterlongo, P (2013) COMPLEXO: identifying the missing heritability of breast cancer via next generation collaboration. Breast Cancer Res 15: pp. 402
40. Hill, SM, Klotz, DM, Cohn, CS Genetics of Breast cancer. In: <span class="editors">Vedeckis, , Wayne, V eds. (1996) Hormone and Cancer. Birkhauser, Bostonpp. 199
41. Xu, X, Wagner, KU, Larson, D, Weaver, Z, Li, C, Ried, T, Hennighausen, L, Wynshaw-Boris, A, Deng, CX (1999) Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation. Nat Genet 22: pp. 37-43 ss="external" href="http://dx.doi.org/10.1038/8743" target="_blank" title="It opens in new window">CrossRef
42. Sherman, S, Shats, O, Fleissner, E, Bascom, G, Yiee, K, Copur, M, Crow, K, Rooney, J, Mateen, Z, Ketcham, MA, Feng, J, Sherman, A, Gleason, M, Kinarsky, L, Silva-Lopez, E, Edney, J, Reed, E, Berger, A, Cowan, K (2011) Multicenter breast cancer collaborative registry. Cancer Inform 10: pp. 217-226 ss="external" href="http://dx.doi.org/10.4137/CIN.S7845" target="_blank" title="It opens in new window">CrossRef
43. The pre-publication history for this paper can be accessed here: ss="a-plus-plus">http://www.biomedcentral.com/1471-2407/14/470/prepub - 刊物主题：Cancer Research; Oncology; Stem Cells; Animal Models; Internal Medicine;
- 出版者：BioMed Central
- ISSN：1471-2407
文摘
Background Genetic predisposition is the primary risk factor for familial breast cancer. For the majority of familial breast cancer, however, the genetic predispositions remain unknown. All newly identified predispositions occur rarely in disease population, and the unknown genetic predispositions are estimated to reach up to total thousands. Family unit is the basic structure of genetics. Because it is an autosomal dominant disease, individuals with a history of familial breast cancer must carry the same genetic predisposition across generations. Therefore, focusing on the cases in lineages of familial breast cancer, rather than pooled cases in disease population, is expected to provide high probability to identify the genetic predisposition for each family. Methods In this study, we tested genetic predispositions by analyzing the family-specific variants in familial breast cancer. Using exome sequencing, we analyzed three families and 22 probands with BRCAx (BRCA-negative) familial breast cancer. Results We observed the presence of family-specific, novel, deleterious germline variants in each family. Of the germline variants identified, many were shared between the disease-affected family members of the same family but not found in different families, which have their own specific variants. Certain variants are putative deleterious genetic predispositions damaging functionally important genes involved in DNA replication and damaging repair, tumor suppression, signal transduction, and phosphorylation. Conclusions Our study demonstrates that the predispositions for many BRCAx familial breast cancer families can lie in each disease family. The application of a family-focused approach has the potential to detect many new predispositions.