A 24-color metaphase-based radiation assay discriminates heterozygous BRCA2 mutation carriers from controls by chromosomal radiosensitivity.
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A 24-color metaphase-based radiation assay discriminates heterozygous BRCA2 mutation carriers from controls by chromosomal radiosensitivity. / Becker, Alexandra A; Graeser, Monika; Landwehr, Christina; Hilger, Thomas; Baus, Wolfgang; Wappenschmidt, Barbara; Meindl, Alfons; Weber, Ruthild G; Schmutzler, Rita K.
in: BREAST CANCER RES TR, Jahrgang 135, Nr. 1, 1, 2012, S. 167-175.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - A 24-color metaphase-based radiation assay discriminates heterozygous BRCA2 mutation carriers from controls by chromosomal radiosensitivity.
AU - Becker, Alexandra A
AU - Graeser, Monika
AU - Landwehr, Christina
AU - Hilger, Thomas
AU - Baus, Wolfgang
AU - Wappenschmidt, Barbara
AU - Meindl, Alfons
AU - Weber, Ruthild G
AU - Schmutzler, Rita K
PY - 2012
Y1 - 2012
N2 - Numerous allelic variants identified in the familial breast cancer and DNA repair genes BRCA1 and BRCA2 are of unknown impact on protein function or clinical relevance, referred to as unclassified variants (UCV). Lymphocytes from pathogenic BRCA1/2 mutation carriers exhibit an increased level of chromosomal damage after irradiation. We established a radiation assay for the discrimination of pathogenic BRCA2 variants versus controls based on the level of chromosomal damage upon irradiation (p < 0.001). As a consequence, lymphocytes from UCV carriers could be separated into two distinct groups with normal or diminished DNA double strand break repair capacity. Our results suggested that all five UCV tested were benign and that one family carried a putative mutation in an as yet undetected DNA-repair gene. Thus, our test may serve as a valuable tool that aids the classification of BRCA2 UCV, but very likely also of BRCA1 UCV or aberrations in other genes involved in the DNA-repair system.
AB - Numerous allelic variants identified in the familial breast cancer and DNA repair genes BRCA1 and BRCA2 are of unknown impact on protein function or clinical relevance, referred to as unclassified variants (UCV). Lymphocytes from pathogenic BRCA1/2 mutation carriers exhibit an increased level of chromosomal damage after irradiation. We established a radiation assay for the discrimination of pathogenic BRCA2 variants versus controls based on the level of chromosomal damage upon irradiation (p < 0.001). As a consequence, lymphocytes from UCV carriers could be separated into two distinct groups with normal or diminished DNA double strand break repair capacity. Our results suggested that all five UCV tested were benign and that one family carried a putative mutation in an as yet undetected DNA-repair gene. Thus, our test may serve as a valuable tool that aids the classification of BRCA2 UCV, but very likely also of BRCA1 UCV or aberrations in other genes involved in the DNA-repair system.
KW - Humans
KW - Female
KW - Middle Aged
KW - Mutation
KW - Heterozygote
KW - Breast Neoplasms/genetics
KW - DNA Repair/genetics
KW - Chromosome Breakage
KW - DNA Breaks, Double-Stranded
KW - BRCA2 Protein/genetics
KW - Chromosomes, Human/radiation effects
KW - Genes, BRCA2
KW - Radiation Tolerance/genetics
KW - Ultraviolet Rays
KW - Humans
KW - Female
KW - Middle Aged
KW - Mutation
KW - Heterozygote
KW - Breast Neoplasms/genetics
KW - DNA Repair/genetics
KW - Chromosome Breakage
KW - DNA Breaks, Double-Stranded
KW - BRCA2 Protein/genetics
KW - Chromosomes, Human/radiation effects
KW - Genes, BRCA2
KW - Radiation Tolerance/genetics
KW - Ultraviolet Rays
M3 - SCORING: Journal article
VL - 135
SP - 167
EP - 175
JO - BREAST CANCER RES TR
JF - BREAST CANCER RES TR
SN - 0167-6806
IS - 1
M1 - 1
ER -
