Sakai, Wataru
([1] Division of Human Biology, [2] Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA)
,
Swisher, Elizabeth M.
([1] Department of Obstetrics and Gynecology, [2] Department of Medicine, University of Washington, Seattle, Washington 98195-7720, USA)
,
Karlan, Beth Y.
(Cedars-Sinai Medical Center, Women’s Cancer Research Institute, Los Angeles, California 90048-1865, USA)
,
Agarwal, Mukesh K.
(Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA)
,
Higgins, Jake
([1] Department of Medicine, University of Washington, Seattle, Washington 98195-7720, USA [2] Department of Genome Sciences, University of Washington, Seattle, Washington 98195-7720, USA)
,
Friedman, Cynthia
(Division of Human Biology,)
,
Villegas, Emily
([1] Division of Human Biology, [2] Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA)
,
Jacquemont, Céline
([1] Division of Human Biology, [2] Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024,)
,
Farrugia, Daniel J.
,
Couch, Fergus J.
,
Urban, Nicole
,
Taniguchi, Toshiyasu
Ovarian carcinomas with mutations in the tumour suppressor BRCA2 are particularly sensitive to platinum compounds. However, such carcinomas ultimately develop cisplatin resistance. The mechanism of that resistance is largely unknown. Here we show that acquired resistance to cisplatin can be mediated...
Ovarian carcinomas with mutations in the tumour suppressor BRCA2 are particularly sensitive to platinum compounds. However, such carcinomas ultimately develop cisplatin resistance. The mechanism of that resistance is largely unknown. Here we show that acquired resistance to cisplatin can be mediated by secondary intragenic mutations in BRCA2 that restore the wild-type BRCA2 reading frame. First, in a cisplatin-resistant BRCA2-mutated breast-cancer cell line, HCC1428, a secondary genetic change in BRCA2 rescued BRCA2 function. Second, cisplatin selection of a BRCA2-mutated pancreatic cancer cell line, Capan-1 (refs 3, 4), led to five different secondary mutations that restored the wild-type BRCA2 reading frame. All clones with secondary mutations were resistant both to cisplatin and to a poly(ADP-ribose) polymerase (PARP) inhibitor (AG14361). Finally, we evaluated recurrent cancers from patients whose primary BRCA2-mutated ovarian carcinomas were treated with cisplatin. The recurrent tumour that acquired cisplatin resistance had undergone reversion of its BRCA2 mutation. Our results suggest that secondary mutations that restore the wild-type BRCA2 reading frame may be a major clinical mediator of acquired resistance to platinum-based chemotherapy.
Ovarian carcinomas with mutations in the tumour suppressor BRCA2 are particularly sensitive to platinum compounds. However, such carcinomas ultimately develop cisplatin resistance. The mechanism of that resistance is largely unknown. Here we show that acquired resistance to cisplatin can be mediated by secondary intragenic mutations in BRCA2 that restore the wild-type BRCA2 reading frame. First, in a cisplatin-resistant BRCA2-mutated breast-cancer cell line, HCC1428, a secondary genetic change in BRCA2 rescued BRCA2 function. Second, cisplatin selection of a BRCA2-mutated pancreatic cancer cell line, Capan-1 (refs 3, 4), led to five different secondary mutations that restored the wild-type BRCA2 reading frame. All clones with secondary mutations were resistant both to cisplatin and to a poly(ADP-ribose) polymerase (PARP) inhibitor (AG14361). Finally, we evaluated recurrent cancers from patients whose primary BRCA2-mutated ovarian carcinomas were treated with cisplatin. The recurrent tumour that acquired cisplatin resistance had undergone reversion of its BRCA2 mutation. Our results suggest that secondary mutations that restore the wild-type BRCA2 reading frame may be a major clinical mediator of acquired resistance to platinum-based chemotherapy.
참고문헌 (39)
Cancer Res. SS Yuan 59 3547 1999 Yuan, S. S. et al. BRCA2 is required for ionizing radiation-induced assembly of Rad51 complex in vivo. Cancer Res. 59, 3547-3551 (1999)
Nature Rev. Cancer R Agarwal 3 502 2003 10.1038/nrc1123 Agarwal, R. & Kaye, S. B. Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nature Rev. Cancer 3, 502-516 (2003)
Cancer Res. M Goggins 56 5360 1996 Goggins, M. et al. Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res. 56, 5360-5364 (1996)
J. Natl Cancer Inst. DW Abbott 90 978 1998 10.1093/jnci/90.13.978 Abbott, D. W., Freeman, M. L. & Holt, J. T. Double-strand break repair deficiency and radiation sensitivity in BRCA2 mutant cancer cells. J. Natl Cancer Inst. 90, 978-985 (1998)
Curr. Oncol. Rep. AJ Li 3 27 2001 10.1007/s11912-001-0039-y Li, A. J. & Karlan, B. Y. Genetic factors in ovarian carcinoma. Curr. Oncol. Rep. 3, 27-32 (2001)
J. Med. Genet. CJ van Asperen 42 711 2005 10.1136/jmg.2004.028829 van Asperen, C. J. et al. Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J. Med. Genet. 42, 711-719 (2005)
Science NG Howlett 297 606 2002 10.1126/science.1073834 Howlett, N. G. et al. Biallelic inactivation of BRCA2 in Fanconi anemia. Science 297, 606-609 (2002)
Mol. Cell ME Moynahan 7 263 2001 10.1016/S1097-2765(01)00174-5 Moynahan, M. E., Pierce, A. J. & Jasin, M. BRCA2 is required for homology-directed repair of chromosomal breaks. Mol. Cell 7, 263-272 (2001)
Cancer Res. SL Neuhausen 54 6069 1994 Neuhausen, S. L. & Marshall, C. J. Loss of heterozygosity in familial tumors from three BRCA1-linked kindreds. Cancer Res. 54, 6069-6072 (1994)
Oncogene N Collins 10 1673 1995 Collins, N. et al. Consistent loss of the wild type allele in breast cancers from a family linked to the BRCA2 gene on chromosome 13q12-13. Oncogene 10, 1673-1675 (1995)
Cancer Res. J Gudmundsson 55 4830 1995 Gudmundsson, J. et al. Different tumor types from BRCA2 carriers show wild-type chromosome deletions on 13q12-q13. Cancer Res. 55, 4830-4832 (1995)
J. Biol. Chem. A Bhattacharyya 275 23899 2000 10.1074/jbc.C000276200 Bhattacharyya, A., Ear, U. S., Koller, B. H., Weichselbaum, R. R. & Bishop, D. K. The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin. J. Biol. Chem. 275, 23899-23903 (2000)
Cold Spring Harb. Symp. Quant. Biol. AN Tutt 70 139 2005 10.1101/sqb.2005.70.012 Tutt, A. N. et al. Exploiting the DNA repair defect in BRCA mutant cells in the design of new therapeutic strategies for cancer. Cold Spring Harb. Symp. Quant. Biol. 70, 139-148 (2005)
Fam. Cancer WD Foulkes 5 135 2006 10.1007/s10689-005-2832-5 Foulkes, W. D. BRCA1 and BRCA2: chemosensitivity, treatment outcomes and prognosis. Fam. Cancer 5, 135-142 (2006)
J. Am. Med. Assoc. J Boyd 283 2260 2000 10.1001/jama.283.17.2260 Boyd, J. et al. Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. J. Am. Med. Assoc. 283, 2260-2265 (2000)
J. Med. Genet. R Hirschhorn 40 721 2003 10.1136/jmg.40.10.721 Hirschhorn, R. In vivo reversion to normal of inherited mutations in humans. J. Med. Genet. 40, 721-728 (2003)
Br. J. Haematol. S Hamanoue 132 630 2006 10.1111/j.1365-2141.2005.05916.x Hamanoue, S. et al. Myeloid lineage-selective growth of revertant cells in Fanconi anaemia. Br. J. Haematol. 132, 630-635 (2006)
Nature Genet. B Xia 39 159 2007 10.1038/ng1942 Xia, B. et al. Fanconi anaemia is associated with a defect in the BRCA2 partner PALB2. Nature Genet. 39, 159-161 (2007)
Int. J. Cancer AF Gazdar 78 766 1998 10.1002/(SICI)1097-0215(19981209)78:6<766::AID-IJC15>3.0.CO;2-L Gazdar, A. F. et al. Characterization of paired tumor and non-tumor cell lines established from patients with breast cancer. Int. J. Cancer 78, 766-774 (1998)
Nature Genet. S Neuhausen 13 126 1996 10.1038/ng0596-126 Neuhausen, S. et al. Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer. Nature Genet. 13, 126-128 (1996)
Proc. Natl Acad. Sci. USA H Saeki 103 8768 2006 10.1073/pnas.0600298103 Saeki, H. et al. Suppression of the DNA repair defects of BRCA2-deficient cells with heterologous protein fusions. Proc. Natl Acad. Sci. USA 103, 8768-8773 (2006)
Cancer Res. K Wu 65 417 2005 10.1158/0008-5472.417.65.2 Wu, K. et al. Functional evaluation and cancer risk assessment of BRCA2 unclassified variants. Cancer Res. 65, 417-426 (2005)
Nature H Farmer 434 917 2005 10.1038/nature03445 Farmer, H. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917-921 (2005)
Nature HE Bryant 434 913 2005 10.1038/nature03443 Bryant, H. E. et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434, 913-917 (2005)
Cancer Res. C Jacquemont 67 7395 2007 10.1158/0008-5472.CAN-07-1015 Jacquemont, C. & Taniguchi, T. Proteasome function is required for DNA damage response and fanconi anemia pathway activation. Cancer Res. 67, 7395-7405 (2007)
EMBO J. A Tutt 20 4704 2001 10.1093/emboj/20.17.4704 Tutt, A. et al. Mutation in Brca2 stimulates error-prone homology-directed repair of DNA double-strand breaks occurring between repeated sequences. EMBO J. 20, 4704-4716 (2001)
J. Natl. Cancer Inst. JL Hilton 94 1396 2002 10.1093/jnci/94.18.1396 Hilton, J. L. et al. Inactivation of BRCA1 and BRCA2 in ovarian cancer. J. Natl. Cancer Inst. 94, 1396-1406 (2002)
Cancer Res. H Ikeda 63 2688 2003 Ikeda, H. et al. Genetic reversion in an acute myelogenous leukemia cell line from a Fanconi anemia patient with biallelic mutations in BRCA2. Cancer Res. 63, 2688-2694 (2003)
Mutat. Res. WW Wiegant 600 79 2006 10.1016/j.mrfmmm.2006.03.001 Wiegant, W. W., Overmeer, R. M., Godthelp, B. C., van Buul, P. P. & Zdzienicka, M. Z. Chinese hamster cell mutant, V-C8, a model for analysis of Brca2 function. Mutat. Res. 600, 79-88 (2006)
Science ME Gorre 293 876 2001 10.1126/science.1062538 Gorre, M. E. et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293, 876-880 (2001)
Nature Med. T Taniguchi 9 568 2003 10.1038/nm852 Taniguchi, T. et al. Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nature Med. 9, 568-574 (2003)
Mol. Cell I Garcia-Higuera 7 249 2001 10.1016/S1097-2765(01)00173-3 Garcia-Higuera, I. et al. Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway. Mol. Cell 7, 249-262 (2001)
Cell T Taniguchi 109 459 2002 10.1016/S0092-8674(02)00747-X Taniguchi, T. et al. Convergence of the Fanconi anemia and ataxia telangiectasia signaling pathways. Cell 109, 459-472 (2002)
Mol. Cancer Ther. D Chirnomas 5 952 2006 10.1158/1535-7163.MCT-05-0493 Chirnomas, D. et al. Chemosensitization to cisplatin by inhibitors of the Fanconi anemia/BRCA pathway. Mol. Cancer Ther. 5, 952-961 (2006)
Mol. Cell. Biol. D Naf 18 5952 1998 10.1128/MCB.18.10.5952 Naf, D., Kupfer, G. M., Suliman, A., Lambert, K. & D’Andrea, A. D. Functional activity of the fanconi anemia protein FAA requires FAC binding and nuclear localization. Mol. Cell. Biol. 18, 5952-5960 (1998)
J. Med. Chem. DJ Skalitzky 46 210 2003 10.1021/jm0255769 Skalitzky, D. J. et al. Tricyclic benzimidazoles as potent poly(ADP-ribose) polymerase-1 inhibitors. J. Med. Chem. 46, 210-213 (2003)
Proc. Natl Acad. Sci. USA T Yamashita 91 6712 1994 10.1073/pnas.91.14.6712 Yamashita, T., Barber, D. L., Zhu, Y., Wu, N. & D’Andrea, A. D. The Fanconi anemia polypeptide FACC is localized to the cytoplasm. Proc. Natl Acad. Sci. USA 91, 6712-6716 (1994)
DNA Repair D Bruun 2 1007 2003 10.1016/S1568-7864(03)00112-5 Bruun, D. et al. siRNA depletion of BRCA1, but not BRCA2, causes increased genome instability in Fanconi anemia cells. DNA Repair 2, 1007-1013 (2003)
BJ Trask 303 1999 Genome Analysis: A Laboratory Manual Trask, B. J. in Genome Analysis: A Laboratory Manual (eds Birren, B. et al.), vol. 4 303-413 (Cold Spring Harbor Laboratory Press, New York, 1999)
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