ATM gene mutations in sporadic breast cancer patients from Brazil

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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Clinical significance of estrogen receptor 1 gene mutations in hormonal resistant breast cancer patients

Gene Reports ◽

10.1016/j.genrep.2021.101261 ◽

2021 ◽

pp. 101261

Author(s):

Reham A. Aboelwafa ◽

Nermine H. Zakaria ◽

Neamat Hagazy ◽

Inas I. Zaki ◽

Aya S. Rady ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Cancer Patients ◽

Clinical Significance ◽

Gene Mutations ◽

Breast Cancer Patients ◽

Estrogen Receptor 1

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Over-representation of a polymorphism/missense mutation in the ataxia telangiectasia, mutated (ATM) gene in breast cancer patients versus controls

European Journal of Cancer ◽

10.1016/s0959-8049(01)81463-5 ◽

2001 ◽

Vol 37 ◽

pp. S262 ◽

Cited By ~ 1

Author(s):

T.A. Buchholz ◽

M.D. Story ◽

C.L. Ashorn ◽

R. Chakraborty ◽

E.A. Strom ◽

...

Keyword(s):

Breast Cancer ◽

Missense Mutation ◽

Cancer Patients ◽

Ataxia Telangiectasia ◽

Breast Cancer Patients ◽

Ataxia Telangiectasia Mutated ◽

Atm Gene

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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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