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

2022 ◽  
Author(s):  
Aglaya G. Iyevleva ◽  
Svetlana N. Aleksakhina ◽  
Anna P. Sokolenko ◽  
Sofia V. Baskina ◽  
Aigul R. Venina ◽  
...  
Keyword(s):  
Chromosomal Instability ◽  
Breast Cancers ◽  
Border Line

Acceleration of Chromosomal Instability of BRCA1-Associated Hereditary Breast Cancers by p53 Abnormality

2002 ◽  
Vol 8 (2) ◽  
pp. 77-80 ◽  
Author(s):  
Yasuo Miyoshi ◽  
Kyoko Iwao ◽  
Noriko Ikeda ◽  
Chiyomi Egawa ◽  
Shinzaburo Noguchi
Keyword(s):  
Chromosomal Instability ◽  
Breast Cancers

A novel prognostic signature based on centrosome amplification-based genes to predict clinical outcomes in breast tumors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11604-11604
Author(s):  
Angela Ogden ◽  
Padmashree C.G. Rida ◽  
Ritu Aneja
Keyword(s):  
Breast Cancer ◽  
Clinical Outcomes ◽  
Chromosomal Instability ◽  
Prognostic Value ◽  
Breast Tumors ◽  
Centrosome Amplification ◽  
Age At Diagnosis ◽  
Breast Cancers ◽  
Cox Models ◽  
Tcga Dataset

11604 Background: A majority of breast tumors exhibit centrosome amplification (CA), which imparts aggressive phenotypes like chromosomal instability and invasive behavior. Nevertheless, it is unclear whether CA is associated with poor clinical outcomes after adjusting for potentially confounding factors, like stage and age at diagnosis. Methods: We developed a twenty-gene signature, “CA20,” composed of genes related to centrosome structure and/or whose dysregulation induces CA and tested its prognostic value compared with that of CIN25, a chromosomal instability (CIN) signature, in combined multivariable Cox models using the METABRIC and TCGA microarray breast datasets. The n = 1,969 primary breast cancers of the METABRIC dataset were split randomly and approximately equally into training and validation sets, unlike the n = 524 primary invasive breast cancers of the TCGA dataset, which could not be split to preserve power ≈ 0.80, so bootstrapping was instead used. CA20 and CIN25 were dichotomized by average scores and optimal cutpoints based on the log-rank test. Results: In both discovery and validation METRABRIC sets, CA20 was a significant independent predictor of worse breast cancer-specific survival (HR = 2.9, p < 0.001 and 2.4, p < 0.001, respectively, using average scores as cutpoints; similar results obtained using optimal cutpoints) in multivariable Cox models, unlike CIN25. CA20 score was highly correlated with CIN25 score (ρ = 0.93, p < 10-6). In the TCGA dataset, high CA20 score was associated with 3.8- and 3.7-fold worse overall survival (bootstrap-p = 0.001 and 0.002, respectively, for average and optimal cutpoints) after adjusting for tumor stage and age at diagnosis, unlike CIN25. Also in the TCGA dataset, CA20 correlated very strongly with CIN25 (ρ = 0.95, p < 10-6). Finally, using the TCGA dataset, we identified processes and pathways enriched in the CA20-high group (q < 0.05) that may be potential therapeutic targets, such as DNA repair processes, the DNA integrity checkpoint, and regulation of microtubule dynamics. Conclusions: CA20 is a novel signature with robust prognostic value in breast cancer and identifies patients who might respond to centrosome declustering drugs.

Immune gene signatures in triple-negative breast cancers characterized by varying levels of chromosomal instability.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1096-1096 ◽  
Author(s):  
Balazs Gyorffy ◽  
Giulia Bottai ◽  
Adam Nagy ◽  
Lajos Pusztai ◽  
Libero Santarpia
Keyword(s):  
T Cells ◽  
Chromosomal Instability ◽  
Triple Negative ◽  
Cytotoxic T Cells ◽  
Nuclear Factor Κb ◽  
Good Prognosis ◽  
Immune Gene ◽  
Breast Cancers ◽  
High Group ◽  
Immune Infiltration

1096 Background: Triple-negative breast cancer (TNBC) is generally characterized by high levels of chromosomal instability (CIN) and an intense immune infiltration. However, the link between these two hallmarks and its implications for clinical practice has not been fully elucidated. Methods: We generated eight immune metagenes representing various immune components: natural killer [NK], dendritic cells [DC], T-cells [TC], B-cells [BC], cytotoxic T-cells [CT], interferon [IFN], nuclear factor-κB [NF-kB], and macrophages [M]. Publicly available gene expression data from forty-two data sets, including 862 TNBC samples, were collected. TNBC tumors were clustered in three main subgroups (Basal-Like [BL1/2], Immunomodulatory [IM], and Mesenchymal/Mesenchymal Stem-Like [MS]) using transcriptomic profiling. The CIN70 signature was used to stratify TNBC patients according to the levels of CIN. Statistical analyses were performed using Mann–Whitney U test and Kaplan-Meier analyses. Results: The majority of TNBC samples showed a high level of CIN (83%), and several immune modules were differentially expressed between CIN-high and CIN-low tumors. Specifically, CT, NK, DC, M, and NF-kB signatures were overexpressed in CIN-low TNBC ( p < 1.0E-04). We then evaluated the distribution of genomic instability among TNBC molecular subgroups. Noteworthy, the CIN-high group was composed by a comparable proportion of BL1/2 (39%) and MS (35%) tumors, while CIN-low TNBCs were consistently enriched for MS cancers (61%). Higher expression of the NK, M, and IFN metagenes lead to better survival in CIN-high tumors ( p = 1.9E-02, p = 2.1E-04, and p = 1.1E-03, respectively). Only IFN had the same correlation to survival in CIN-low ( p = 1.4E-02). Conclusions: TNBCs with low levels of CIN may principally enclose M/MSL tumors, which are characterized by an intense immune infiltration and overall good prognosis. Conversely, the TNBC CIN-high group is more heterogeneous in terms of both biological features and levels of immune infiltrates. Therapeutic strategies to promote and boost immune response in the genomically unstable TNBC subgroup warrant further investigation.

Association of centrosomal kinaseSTK15/BTAK mRNA expression with chromosomal instability in human breast cancers

2001 ◽  
Vol 92 (3) ◽  
pp. 370-373 ◽  
Author(s):  
Yasuo Miyoshi ◽  
Kyoko Iwao ◽  
Chiyomi Egawa ◽  
Shinzaburo Noguchi
Keyword(s):  
Mrna Expression ◽  
Chromosomal Instability ◽  
Breast Cancers ◽  
Human Breast
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