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Acquired cross-linker resistance associated with a novel spliced BRCA2 protein variant for molecular phenotyping of BRCA2 disruption

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Acquired cross-linker resistance associated with a novel spliced BRCA2 protein variant for molecular phenotyping of BRCA2 disruption. / Meyer, Stefan; Stevens, Adam; Paredes, Roberto et al.
In: Cell Death and Disease, Vol. 8, No. 6, 2017, p. e2875-e2875.

Research output: Contribution to journal › Article › peer-review

HarvardHarvard

Meyer, S, Stevens, A, Paredes, R, Schneider, M, Walker, MJ, Williamson, AJK, Gonzalez-Sanchez, M-B, Smetsers, S, Dalal, V, Teng, HY, White, DJ, Taylor, S, Muter, J, Pierce, A, de Leonibus, C, Rockx, DAP, Rooimans, MA, Spooncer, E, Stauffer, S, Biswas, K, Godthelp, B, Dorsman, J, Clayton, PE, Sharan, SK & Whetton, AD 2017, 'Acquired cross-linker resistance associated with a novel spliced BRCA2 protein variant for molecular phenotyping of BRCA2 disruption', Cell Death and Disease, vol. 8, no. 6, pp. e2875-e2875. https://doi.org/10.1038/cddis.2017.264

APA

Meyer, S., Stevens, A., Paredes, R., Schneider, M., Walker, M. J., Williamson, A. J. K., Gonzalez-Sanchez, M.-B., Smetsers, S., Dalal, V., Teng, H. Y., White, D. J., Taylor, S., Muter, J., Pierce, A., de Leonibus, C., Rockx, D. A. P., Rooimans, M. A., Spooncer, E., Stauffer, S., ... Whetton, A. D. (2017). Acquired cross-linker resistance associated with a novel spliced BRCA2 protein variant for molecular phenotyping of BRCA2 disruption. Cell Death and Disease, 8(6), e2875-e2875. https://doi.org/10.1038/cddis.2017.264

CBE

Meyer S, Stevens A, Paredes R, Schneider M, Walker MJ, Williamson AJK, Gonzalez-Sanchez M-B, Smetsers S, Dalal V, Teng HY, et al. 2017. Acquired cross-linker resistance associated with a novel spliced BRCA2 protein variant for molecular phenotyping of BRCA2 disruption. Cell Death and Disease. 8(6):e2875-e2875. https://doi.org/10.1038/cddis.2017.264

MLA

Meyer, Stefan et al. "Acquired cross-linker resistance associated with a novel spliced BRCA2 protein variant for molecular phenotyping of BRCA2 disruption". Cell Death and Disease. 2017, 8(6). e2875-e2875. https://doi.org/10.1038/cddis.2017.264

VancouverVancouver

Meyer S, Stevens A, Paredes R, Schneider M, Walker MJ, Williamson AJK et al. Acquired cross-linker resistance associated with a novel spliced BRCA2 protein variant for molecular phenotyping of BRCA2 disruption. Cell Death and Disease. 2017;8(6):e2875-e2875. doi: 10.1038/cddis.2017.264

Author

Meyer, Stefan ; Stevens, Adam ; Paredes, Roberto et al. / Acquired cross-linker resistance associated with a novel spliced BRCA2 protein variant for molecular phenotyping of BRCA2 disruption. In: Cell Death and Disease. 2017 ; Vol. 8, No. 6. pp. e2875-e2875.

RIS

TY - JOUR

T1 - Acquired cross-linker resistance associated with a novel spliced BRCA2 protein variant for molecular phenotyping of BRCA2 disruption

AU - Meyer, Stefan

AU - Stevens, Adam

AU - Paredes, Roberto

AU - Schneider, Marion

AU - Walker, Michael J

AU - Williamson, Andrew J K

AU - Gonzalez-Sanchez, Maria-Belen

AU - Smetsers, Stephanie

AU - Dalal, Vineet

AU - Teng, Hsiang Ying

AU - White, Daniel J

AU - Taylor, Sam

AU - Muter, Joanne

AU - Pierce, Andrew

AU - de Leonibus, Chiara

AU - Rockx, Davy A P

AU - Rooimans, Martin A

AU - Spooncer, Elaine

AU - Stauffer, Stacey

AU - Biswas, Kajal

AU - Godthelp, Barbara

AU - Dorsman, Josephine

AU - Clayton, Peter E

AU - Sharan, Shyam K

AU - Whetton, Anthony D

PY - 2017

Y1 - 2017

N2 - BRCA2 encodes a protein with a fundamental role in homologous recombination that is essential for normal development. Carrier status of mutations in BRCA2 is associated with familial breast and ovarian cancer, while bi-allelic BRCA2 mutations can cause Fanconi anemia (FA), a cancer predisposition syndrome with cellular cross-linker hypersensitivity. Cancers associated with BRCA2 mutations can acquire chemo-resistance on relapse. We modeled acquired cross-linker resistance with an FA-derived BRCA2-mutated acute myeloid leukemia (AML) platform. Associated with acquired cross-linker resistance was the expression of a functional BRCA2 protein variant lacking exon 5 and exon 7 (BRCA2ΔE5+7), implying a role for BRCA2 splicing for acquired chemo-resistance. Integrated network analysis of transcriptomic and proteomic differences for phenotyping of BRCA2 disruption infers impact on transcription and chromatin remodeling in addition to the DNA damage response. The striking overlap with transcriptional profiles of FA patient hematopoiesis and BRCA mutation associated ovarian cancer helps define and explicate the ‘BRCAness’ profile.

AB - BRCA2 encodes a protein with a fundamental role in homologous recombination that is essential for normal development. Carrier status of mutations in BRCA2 is associated with familial breast and ovarian cancer, while bi-allelic BRCA2 mutations can cause Fanconi anemia (FA), a cancer predisposition syndrome with cellular cross-linker hypersensitivity. Cancers associated with BRCA2 mutations can acquire chemo-resistance on relapse. We modeled acquired cross-linker resistance with an FA-derived BRCA2-mutated acute myeloid leukemia (AML) platform. Associated with acquired cross-linker resistance was the expression of a functional BRCA2 protein variant lacking exon 5 and exon 7 (BRCA2ΔE5+7), implying a role for BRCA2 splicing for acquired chemo-resistance. Integrated network analysis of transcriptomic and proteomic differences for phenotyping of BRCA2 disruption infers impact on transcription and chromatin remodeling in addition to the DNA damage response. The striking overlap with transcriptional profiles of FA patient hematopoiesis and BRCA mutation associated ovarian cancer helps define and explicate the ‘BRCAness’ profile.

U2 - 10.1038/cddis.2017.264

DO - 10.1038/cddis.2017.264

M3 - Article

VL - 8

SP - e2875-e2875

JO - Cell Death and Disease

JF - Cell Death and Disease

SN - 2041-4889

IS - 6

ER -