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

Cancers ◽  
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.

BRCA gene mutations in Slovenian male breast cancer patients

2007 ◽  
Vol 4 (03) ◽  
Author(s):  
N Besic ◽  
B Cernivc ◽  
J De Greve ◽  
K Lokar ◽  
M Krajc ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Male Breast Cancer ◽  
Gene Mutations ◽  
Male Breast ◽  
Breast Cancer Patients ◽  
Brca Gene

scholarly journals Mapping of Genomic Vulnerabilities in the Post-Translational Ubiquitination, SUMOylation and Neddylation Machinery in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 833
Author(s):  
Jesús Fuentes-Antrás ◽  
Ana Lucía Alcaraz-Sanabria ◽  
Esther Cabañas Morafraile ◽  
María del Mar Noblejas-López ◽  
Eva María Galán-Moya ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Development ◽  
Gene Mutations ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Clinical Value ◽  
Luminal A ◽  
Genomic Alterations ◽  
Cancer Hallmarks ◽  
Worse Prognosis

The dysregulation of post-translational modifications (PTM) transversally impacts cancer hallmarks and constitutes an appealing vulnerability for drug development. In breast cancer there is growing preclinical evidence of the role of ubiquitin and ubiquitin-like SUMO and Nedd8 peptide conjugation to the proteome in tumorigenesis and drug resistance, particularly through their interplay with estrogen receptor signaling and DNA repair. Herein we explored genomic alterations in these processes using RNA-seq and mutation data from TCGA and METABRIC datasets, and analyzed them using a bioinformatic pipeline in search of those with prognostic and predictive capability which could qualify as subjects of drug research. Amplification of UBE2T, UBE2C, and BIRC5 conferred a worse prognosis in luminal A/B and basal-like tumors, luminal A/B tumors, and luminal A tumors, respectively. Higher UBE2T expression levels were predictive of a lower rate of pathological complete response in triple negative breast cancer patients following neoadjuvant chemotherapy, whereas UBE2C and BIRC5 expression was higher in luminal A patients with tumor relapse within 5 years of endocrine therapy or chemotherapy. The transcriptomic signatures of USP9X and USP7 gene mutations also conferred worse prognosis in luminal A, HER2-enriched, and basal-like tumors, and in luminal A tumors, respectively. In conclusion, we identified and characterized the clinical value of a group of genomic alterations in ubiquitination, SUMOylation, and neddylation enzymes, with potential for drug development in breast cancer.

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

Gene Reports ◽  
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

scholarly journals Analysis of ESR1 and PIK3CA mutations in plasma cell-free DNA from ER-positive breast cancer patients

Oncotarget ◽  
2017 ◽  
Vol 8 (32) ◽  
pp. 52142-52155 ◽  
Author(s):  
Takashi Takeshita ◽  
Yutaka Yamamoto ◽  
Mutsuko Yamamoto-Ibusuki ◽  
Mai Tomiguchi ◽  
Aiko Sueta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Plasma Cell ◽  
Breast Cancer Patients ◽  
Cell Free Dna ◽  
Pik3ca Mutations ◽  
Free Dna ◽  
Er Positive ◽  
Positive Breast Cancer

Relationship between tumor size and metastatic site in patients with stage IV breast cancer: A large SEER-based study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13065-e13065
Author(s):  
Qian Dong ◽  
Mi Zhang ◽  
Da Jiang
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Size ◽  
Stage Iv ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Chi Square ◽  
Metastatic Site ◽  
Luminal B ◽  
Stage Iv Breast Cancer

e13065 Background: To analyze the correlation between tumor size and metastatic site in first-diagnosed stage IV breast cancer patients. Methods: Stage IV breast cancer patients diagnosed from 2010 to 2015 were screened by the Surveillance, Epidemiology, and End Results (SEER) database. The characteristics of clinical variables were represented by a frequency table, and the Chi-square test was used for comparison. At the same time, the Chi-square test was used to analyze the relationship between tumor size and organ metastasis. Correlation between tumor size and the prognosis of patients was contributed by KM curve and Log-rank test. Results: Regardless of tumor size, the proportion of bone metastasis was higher and brain metastasis was lower in breast cancer patients. There were significant differences in the site of metastases based on different subtype. Luminal A and Luminal B breast cancer had the highest proportion of bone metastases; brain metastasis accounted for the highest proportion in triple-negative breast cancer (TNBC); while the incidence of liver metastasis was the highest in Her-2(+) breast cancer. At the same time, the results indicated that Luminal A breast cancer with a tumor size > 5 cm was more likely to develop multi-site metastasis and lung metastasis, while Luminal B breast cancer with a tumor size ≤ 5 cm was more likely to develop liver metastasis. The results also revealed that TNBC patients with a tumor size of 0 - 2cm were more likely to develop bone metastasis than those with a tumor size > 5 cm, and the incidence of lung metastasis in triple-negative patients showed an increasing trend with the increase of tumor size. Conclusions: Based on subtype, we found that there was a significant difference between tumor size and metastatic site in patients with stage IV breast cancer, and the difference was statistically significant. This study provided evidence-based basis for decision-making of stage IV breast cancer treatment.

Áp dụng hóa bảng phân loại của ST GALLEN 2013 trong phân nhóm phân tử ung thư vú biểu mô tuyến vú

2020 ◽  
Author(s):  
Chu Nguyen Van
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Cancer Patients ◽  
Molecular Classification ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Prognostic Information ◽  
Patient Groups

Molecular classification of breast cancer is target to category patient groups who need to treat by the appropriate adjuvant therapy and provide more exact prognostic information. Purpose: Determining the proportion of molecular types and commenting on some association with clinicpathological characteristics of breast cancer. Methods: 521 operated breast cancer patients were stained by immunohistochemistry with markes such as: ER, PR, HER2, and Ki67 for classifying into 5 molecular categories and follow up assessment. Results: Type LUMBH- accounted for the highest proportion of 26.5%, followed by luminal A (22.5%). Typically, LUMA was the highest rate in good NPI (35.0%), whereas in poor NPI group, HER2 type was the highest rate (36.4%) (p<0.001). The LUMBH - group has the OS rate during the 5-year follow-up of 94.6% and LUMA is 93.5%; In contrast, the HER2 group showed the lowest OS ratio (72.6%) (p<0.05). Conclusion: Molecular classification of breast cancer according to St Gallen 2013 classification can provide the important information for treatment and prognosis.

Sign in / Sign up

Export Citation Format

Share Document