Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Somatic loss of the remaining allele occurs approximately in half of CHEK2-driven breast cancers and is accompanied by a border-line increase of chromosomal instability. / Iyevleva, Aglaya G; Aleksakhina, Svetlana N; Sokolenko, Anna P; Baskina, Sofia V; Venina, Aigul R; Anisimova, Elena I; Bizin, Ilya V; Ivantsov, Alexandr O; Belysheva, Yana V; Chernyakova, Alexandra P; Togo, Alexandr V; Imyanitov, Evgeny N.
в: Breast Cancer Research and Treatment, Том 192, № 2, 04.2022, стр. 283-291.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
}
TY - JOUR
T1 - Somatic loss of the remaining allele occurs approximately in half of CHEK2-driven breast cancers and is accompanied by a border-line increase of chromosomal instability
AU - Iyevleva, Aglaya G
AU - Aleksakhina, Svetlana N
AU - Sokolenko, Anna P
AU - Baskina, Sofia V
AU - Venina, Aigul R
AU - Anisimova, Elena I
AU - Bizin, Ilya V
AU - Ivantsov, Alexandr O
AU - Belysheva, Yana V
AU - Chernyakova, Alexandra P
AU - Togo, Alexandr V
AU - Imyanitov, Evgeny N
N1 - Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022/4
Y1 - 2022/4
N2 - PURPOSE: Germline mutations in CHEK2 gene represent the second most frequent cause of hereditary breast cancer (BC) after BRCA1/2 lesions. This study aimed to identify the molecular characteristics of CHEK2-driven BCs.METHODS: Loss of heterozygosity (LOH) for the remaining CHEK2 allele was examined in 50 CHEK2-driven BCs using allele-specific PCR assays for the germline mutations and analysis of surrounding single-nucleotide polymorphisms (SNPs). Paired tumor and normal DNA samples from 25 cases were subjected to next-generation sequencing analysis.RESULTS: CHEK2 LOH was detected in 28/50 (56%) BCs. LOH involved the wild-type allele in 24 BCs, mutant CHEK2 copy was deleted in 3 carcinomas, while in one case the origin of the deleted allele could not be identified. Somatic PIK3CA and TP53 mutations were present in 13/25 (52%) and 4/25 (16%) tumors, respectively. Genomic features of homologous recombination deficiency (HRD), including the HRD score ≥ 42, the predominance of BRCA-related mutational signature 3, and the high proportion of long (≥ 5 bp) indels, were observed only in 1/20 (5%) BC analyzed for chromosomal instability. Tumors with the deleted wild-type CHEK2 allele differed from LOH-negative cases by elevated HRD scores (median 23 vs. 7, p = 0.010) and higher numbers of chromosomal segments affected by copy number aberrations (p = 0.008).CONCLUSION: Somatic loss of the wild-type CHEK2 allele is observed in approximately half of CHEK2-driven BCs. Tumors without CHEK2 LOH are chromosomally stable. BCs with LOH demonstrate some signs of chromosomal instability; however, its degree is significantly lower as compared to BRCA1/2-associated cancers.
AB - PURPOSE: Germline mutations in CHEK2 gene represent the second most frequent cause of hereditary breast cancer (BC) after BRCA1/2 lesions. This study aimed to identify the molecular characteristics of CHEK2-driven BCs.METHODS: Loss of heterozygosity (LOH) for the remaining CHEK2 allele was examined in 50 CHEK2-driven BCs using allele-specific PCR assays for the germline mutations and analysis of surrounding single-nucleotide polymorphisms (SNPs). Paired tumor and normal DNA samples from 25 cases were subjected to next-generation sequencing analysis.RESULTS: CHEK2 LOH was detected in 28/50 (56%) BCs. LOH involved the wild-type allele in 24 BCs, mutant CHEK2 copy was deleted in 3 carcinomas, while in one case the origin of the deleted allele could not be identified. Somatic PIK3CA and TP53 mutations were present in 13/25 (52%) and 4/25 (16%) tumors, respectively. Genomic features of homologous recombination deficiency (HRD), including the HRD score ≥ 42, the predominance of BRCA-related mutational signature 3, and the high proportion of long (≥ 5 bp) indels, were observed only in 1/20 (5%) BC analyzed for chromosomal instability. Tumors with the deleted wild-type CHEK2 allele differed from LOH-negative cases by elevated HRD scores (median 23 vs. 7, p = 0.010) and higher numbers of chromosomal segments affected by copy number aberrations (p = 0.008).CONCLUSION: Somatic loss of the wild-type CHEK2 allele is observed in approximately half of CHEK2-driven BCs. Tumors without CHEK2 LOH are chromosomally stable. BCs with LOH demonstrate some signs of chromosomal instability; however, its degree is significantly lower as compared to BRCA1/2-associated cancers.
KW - CHEK2 mutation
KW - Hereditary breast cancer
KW - Homologous recombination deficiency
KW - Loss of heterozygosity
KW - CHEK2-ASTERISK-1100DELC
KW - 1100DELC
KW - TUMOR CHARACTERISTICS
KW - WOMEN
KW - REPAIR
KW - GENE
KW - INCREASED RISK
KW - CHEK2
KW - MUTATION
KW - RESISTANT PROSTATE-CANCER
KW - Checkpoint Kinase 2/genetics
KW - Humans
KW - Loss of Heterozygosity
KW - Alleles
KW - Germ-Line Mutation
KW - Female
KW - Breast Neoplasms/genetics
KW - Chromosomal Instability
UR - https://proxy.library.spbu.ru:2096/article/10.1007%2Fs10549-022-06517-3#citeas
UR - http://www.scopus.com/inward/record.url?scp=85122744604&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/5bcaab9c-7c10-3395-a447-9b0d0e53ea4d/
U2 - 10.1007/s10549-022-06517-3
DO - 10.1007/s10549-022-06517-3
M3 - Article
C2 - 35020107
VL - 192
SP - 283
EP - 291
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 2
ER -
ID: 91805277