Copy number alterations of the H2AFX gene in sporadic breast cancer patients

Breast cancer is one of the main causes of cancer death among South African women. Although several risk factors can be attributed to the observed high mortality rate, the biology of the tumors is not extensively investigated. Copy number gain of the DLX4 homeobox gene has been observed in breast cancer in association with poor prognosis and specific racial groups. Therefore, we aimed to assess the copy number and prognostic role of DLX4 in breast cancer from South African patients. Due to the co-location of ERBB2 and DLX4 in the 17q21 region, its copy number was also evaluated. Our results in the analysis of 66 cases demonstrated copy number gains of DLX4 and ERBB2 in 24.1 and 29.7% of the cases, respectively. Linear regression analysis showed no dependency between the copy number alterations in these genes. Although not significant, patients with DLX4 and ERBB2 gains presented a higher frequency of advanced-grade tumors. In addition, copy number alterations of these genes were not significantly differently observed in the 3 main racial groups of the Western Cape population: Colored, White, and Black. These findings indicate that gains of DLX4 and ERBB2 occur in South African breast cancer patients irrespectively of their race and factors known to influence prognosis.

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Integration of DNA Copy Number Alterations and Prognostic Gene Expression Signatures in Breast Cancer Patients

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-09-0709 ◽

2010 ◽

Vol 16 (2) ◽

pp. 651-663 ◽

Cited By ~ 46

Author(s):

Hugo M. Horlings ◽

Carmen Lai ◽

Dimitry S.A. Nuyten ◽

Hans Halfwerk ◽

Petra Kristel ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Patients ◽

Copy Number ◽

Copy Number Alterations ◽

Breast Cancer Patients ◽

Dna Copy Number ◽

Prognostic Gene ◽

Gene Expression Signatures ◽

Dna Copy Number Alterations

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Single Cell Genetic Profiling of Tumors of Breast Cancer Patients Aged 50 Years and Older Reveals Enormous Intratumor Heterogeneity Independent of Individual Prognosis

Cancers ◽

10.3390/cancers13133366 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3366

Author(s):

Anna-Sophie Liegmann ◽

Kerstin Heselmeyer-Haddad ◽

Annette Lischka ◽

Daniela Hirsch ◽

Wei-Dong Chen ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Copy Number ◽

Genome Instability ◽

Single Cells ◽

Gene Mutations ◽

Intratumor Heterogeneity ◽

Breast Cancer Patients ◽

Luminal A ◽

Pik3ca Mutations

Purpose: Older breast cancer patients are underrepresented in cancer research even though the majority (81.4%) of women dying of breast cancer are 55 years and older. Here we study a common phenomenon observed in breast cancer which is a large inter- and intratumor heterogeneity; this poses a tremendous clinical challenge, for example with respect to treatment stratification. To further elucidate genomic instability and tumor heterogeneity in older patients, we analyzed the genetic aberration profiles of 39 breast cancer patients aged 50 years and older (median 67 years) with either short (median 2.4 years) or long survival (median 19 years). The analysis was based on copy number enumeration of eight breast cancer-associated genes using multiplex interphase fluorescence in situ hybridization (miFISH) of single cells, and by targeted next-generation sequencing of 563 cancer-related genes. Results: We detected enormous inter- and intratumor heterogeneity, yet maintenance of common cancer gene mutations and breast cancer specific chromosomal gains and losses. The gain of COX2 was most common (72%), followed by MYC (69%); losses were most prevalent for CDH1 (74%) and TP53 (69%). The degree of intratumor heterogeneity did not correlate with disease outcome. Comparing the miFISH results of diploid with aneuploid tumor samples significant differences were found: aneuploid tumors showed significantly higher average signal numbers, copy number alterations (CNAs) and instability indices. Mutations in PIKC3A were mostly restricted to luminal A tumors. Furthermore, a significant co-occurrence of CNAs of DBC2/MYC, HER2/DBC2 and HER2/TP53 and mutual exclusivity of CNAs of HER2 and PIK3CA mutations and CNAs of CCND1 and PIK3CA mutations were revealed. Conclusion: Our results provide a comprehensive picture of genome instability profiles with a large variety of inter- and intratumor heterogeneity in breast cancer patients aged 50 years and older. In most cases, the distribution of chromosomal aneuploidies was consistent with previous results; however, striking exceptions, such as tumors driven by exclusive loss of chromosomes, were identified.

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Reduced mitochondrial DNA copy number is correlated with tumor progression and prognosis in Chinese breast cancer patients

IUBMB Life ◽

10.1080/15216540701509955 ◽

2007 ◽

Vol 59 (7) ◽

pp. 450-457 ◽

Cited By ~ 156

Author(s):

Man Yu ◽

Yunli Zhou ◽

Yurong Shi ◽

Liansheng Ning ◽

Yi Yang ◽

...

Keyword(s):

Breast Cancer ◽

Mitochondrial Dna ◽

Tumor Progression ◽

Cancer Patients ◽

Copy Number ◽

Breast Cancer Patients ◽

Dna Copy Number ◽

Mitochondrial Dna Copy Number

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Genome-Wide Dna Copy Number Profiles Identify Lapatinib Sensitivity in Metastatic Breast Cancer Patients

Annals of Oncology ◽

10.1093/annonc/mdt083.8 ◽

2013 ◽

Vol 24 ◽

pp. iii25

Author(s):

M. Xie ◽

C. He

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Copy Number ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Dna Copy Number ◽

Genome Wide

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Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) variants and breast cancer risk in Burkina Faso

BioMolecular Concepts ◽

10.1515/bmc-2019-0020 ◽

2019 ◽

Vol 10 (1) ◽

pp. 175-183 ◽

Cited By ~ 1

Author(s):

Isabelle Touwendpoulimdé Kiendrebeogo ◽

Abdou Azaque Zoure ◽

Pegdwendé Abel Sorgho ◽

Albert Théophane Yonli ◽

Florencia Wendkuuni Djigma ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cancer Patients ◽

Sporadic Breast Cancer ◽

Disease Stage ◽

Breast Cancer Patients ◽

Glutathione S Transferase ◽

Increased Risk ◽

Increased Susceptibility

AbstractBackground and objectiveBreast cancer remains the most common cause of cancer mortality in women. The aim of this study was to investigate associations between genetic variability in GSTM1 and GSTT1 and susceptibility to breast cancer.MethodsGenomic DNA was extracted from blood samples for 80 cases of histologically diagnosed breast cancer and 100 control subjects. Genotyping analyses were performed by PCR-based methods. Associations between specific genotypes and the development of breast cancer were examined using logistic regression to calculate odds ratios [1] and 95% confidence intervals (95%CI).ResultsNo correlation was found between GSTM1-null and breast cancer (OR = 1.83; 95%CI 0.90-3.71; p = 0.10), while GSTT1-null (OR = 2.42; 95%CI 1.17-5.02; p= 0.01) was associated with increased breast cancer risk. The GSTM1/GSTT1 double null was not associated with an increased risk of developing breast cancer (OR = 2.52; 95%CI 0.75-8.45; p = 0.20). Furthermore, analysis found no association between GSTM1-null (OR =1.12; 95%CI 0.08-15.50; p = 1.00) or GSTT1-null (OR = 1.71; 95%CI 0.13-22.51; p = 1.00) and the disease stage of familial breast cancer patients or sporadic breast cancer patients (GSTM1 (OR = 0.40; 95%CI 0.12-1.32; p = 0.20) and GSTT1 (OR = 1.41; 95%CI 0.39-5.12; p = 0.75)). Also, body mass index (BMI) was not associated with increased or decreased breast cancer risk in either GSTM1-null (OR = 0.60; 95%CI 0.21-1.68; p = 0.44) or GSTT1-null (OR = 0.60; 95%CI 0.21-1.68; p =0.45).ConclusionOur results suggest that only GSTT1-null is associated with increased susceptibility to breast cancer development.

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