scholarly journals Somatic Mutational Profile of High-Grade Serous Ovarian Carcinoma and Triple-Negative Breast Carcinoma in Young and Elderly Patients: Similarities and Divergences

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3586
Author(s):  
Pedro Adolpho de Menezes Pacheco Serio ◽  
Gláucia Fernanda de Lima Pereira ◽  
Maria Lucia Hirata Katayama ◽  
Rosimeire Aparecida Roela ◽  
Simone Maistro ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Triple Negative ◽  
Median Number ◽  
High Grade ◽  
Cancer Gene ◽  
Driver Genes ◽  
Mutational Signature ◽  
Triple Negative Breast Carcinoma ◽  
Candidate Cancer Gene ◽  
Gene Database

Background: Triple-negative breast cancer (TNBC) and High-Grade Serous Ovarian Cancer (HGSOC) are aggressive malignancies that share similarities; however, different ages of onset may reflect distinct tumor behaviors. Thus, our aim was to compare somatic mutations in potential driver genes in 109 TNBC and 81 HGSOC from young (Y ≤ 40 years) and elderly (E ≥ 75 years) patients. Methods: Open access mutational data (WGS or WES) were collected for TNBC and HGSOC patients. Potential driver genes were those that were present in the Cancer Gene Census—CGC, the Candidate Cancer Gene Database—CCGD, or OncoKB and those that were considered pathogenic in variant effect prediction tools. Results: Mutational signature 3 (homologous repair defects) was the only gene that was represented in all four subgroups. The median number of mutated CGCs per sample was similar in HGSOC (Y:3 vs. E:4), but it was higher in elderly TNBC than it was in young TNBC (Y:3 vs. E:6). At least 90% of the samples from TNBC and HGSOC from Y and E patients presented at least one known affected TSG. Besides TP53, which was mutated in 67–83% of the samples, the affected TSG in TP53 wild-type samples were NF1 (yHGSOC and yTNBC), PHF6 (eHGSOC and yTNBC), PTEN, PIK3R1 and ZHFX3 (yTNBC), KMT2C, ARID1B, TBX3, and ATM (eTNBC). A few samples only presented one affected oncogene (but no TSG): KRAS and TSHR in eHGSOC and RAC1 and PREX2 (a regulator of RAC1) in yTNBC. At least ⅔ of the tumors presented mutated oncogenes associated with tumor suppressor genes; the Ras and/or PIK3CA signaling pathways were altered in 15% HGSOC and 20–35% TNBC (Y vs. E); DNA repair genes were mutated in 19–33% of the HGSOC tumors but were more frequently mutated in E-TNBC (56%). However, in HGSOC, 9.5% and 3.3% of the young and elderly patients, respectively, did not present any tumors with an affected CGC nor did 4.65% and none of the young and elderly TNBC patients. Conclusion: Most HGSOC and TNBC from young and elderly patients present an affected TSG, mainly TP53, as well as mutational signature 3; however, a few tumors only present an affected oncogene or no affected cancer-causing genes.

Somatic mutations in triple-negative breast carcinoma and high-grade serous ovarian carcinoma from young women.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12561-e12561
Author(s):  
Pedro Adolpho MP Serio ◽  
Glaucia Fernanda Lima Pereira ◽  
Maria Lucia Hirata Katayama ◽  
Simone Maistro ◽  
Rossana Veronica Mendoza Lopez ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Somatic Mutations ◽  
Triple Negative ◽  
Young Patients ◽  
High Grade ◽  
Cancer Gene ◽  
Sequencing Data ◽  
Driver Genes ◽  
Cancer Driver ◽  
Serous Ovarian Carcinoma

e12561 Background: High grade serous ovarian carcinoma (HGSOvCa) and triple negative breast cancer (TNBC) share characteristics, such as poor prognosis, BRCA1 germline mutations and TP53 somatic mutations. Our aim was to analyze somatic mutations from HGS-OvCa and TNBC from young patients aged ≤ 40 years. Methods: Whole genome or exome sequencing data for TNBC (n = 83) or HGS-OvCa (n = 21) was recovered from COSMIC or cBioPortal. Data was searched for cancer driver genes catalogued in Cancer Gene Census (CGC) or Candidate Cancer Gene Database rank A or B (CCGD) and for DNA repair genes. Results: TNBC mainly consisted of ductal carcinomas (78/83). A median of two cancer causing genes was affected in both TNBC and HGS-OvCa and TP53 was mutated in at least 2/3 of the samples. Only 7/83 and 2/19 of TNBC and HGS-OvCa samples, respectively, did not present variants in known cancer causing genes. C > T substitutions were the most frequent events in both TNBC and HGS-OvCa, however transversions were more frequently detected in TNBC. Besides TP53, another 33 genes were mutated in both tumor types, including PIK3CA, RYR2, TARBP1, CSMD3, DNAH11, MYO3A, NF1, TNRC6A, CACNA1E, HCMN1, PRKDC. Conclusions: Although many similarities were detected, TNBC in young patients presents a higher number of transversions and almost 25% of HGSOvCa present somatic mutations in HR genes. [Table: see text]

Profile of somatic mutations in young adults with pancreatic cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15790-e15790
Author(s):  
Livia Munhoz Rodrigues ◽  
Simone Maistro ◽  
Maria Lucia Hirata Katayama ◽  
Rosimeire Aparecida Roela ◽  
Maria A. A. Koike Folgueira
Keyword(s):  
Pancreatic Cancer ◽  
Young Adults ◽  
Somatic Mutations ◽  
Cancer Gene ◽  
Driver Genes ◽  
Cancer Driver ◽  
Three Samples ◽  
Candidate Cancer Gene ◽  
Gene Database ◽  
Carcinogenic Process

e15790 Background: Most pancreatic carcinomas (PC) occur in older people, however a few cases are detected in young adults. In this age group, the carcinogenic process is less well understood. Our goal was to identify and to characterize cancer driver genes in early age onset PC. Methods: Somatic variants of individuals affected by PC aged ≤45 years were searched in the COSMIC and CBioPortal databases. The variants were annotated using Oncotator, excluding the silent and intronic variants. Implication in cancer causality was evaluated in the Cancer Gene Census (CGC) and the Candidate Cancer Gene Database (CCGD). The most frequently mutated genes were identified and investigated to determine if they configured FrequentLy mutAted GeneS (FLAGs). Results: Whole genome (4) or exome (29) sequencing was available from 33 individuals (14 females and 19 males). A median of 31 (7-102) alterations per tumor, mainly represented by C > T substitutions (median 16, 2-71), was detected. A median of 3 (0-11) truncated alterations, 4 (1-13) genes cataloged as CGC and 8 (1-22) genes cataloged as CCGD rank A or B was identified per tumor. The most frequently affected genes were those characteristic of tumor promotion in pancreatic cancer carcinogenesis, such as KRAS (79%), TP53 (64%), SMAD4 (18%), followed by RYR1 (15%) and TTN (12%) genes, the latter two classified as FLAGs and, finally, HERC2, GREB1 and DMBT1 (9%). Seventeen samples presented variants in both TP53 and KRAS (17/33), 9 and 4 presented only KRAS or TP53 variants, respectively. Three samples with mutations in neither of these genes presented mutations in genes such as BCLAF1, DCC, BRAF, CDH11 and CDKN2A, both CGCs. Three out of 9 samples carrying KRAS but not TP53 mutations presented variants in DNA homologous repair (HHR) genes. Among all the altered genes, the main biological processes were cell adhesion (139 genes involved) and anatomical structure formation involved in morphogenesis (127), while the most enriched pathways were Wnt (45) and Cadherin (30). Conclusions: TP53 and KRAS are the somatic mutations most frequently detected in PC. 10% of the samples showed no change in these genes, but showed changes in other CGCs. HERC2, GREB1 and DMBT1 are potential cancer drivers in young adult PCs.

scholarly journals The Candidate Cancer Gene Database: a database of cancer driver genes from forward genetic screens in mice

2014 ◽  
Vol 43 (D1) ◽  
pp. D844-D848 ◽  
Author(s):  
Kenneth L. Abbott ◽  
Erik T. Nyre ◽  
Juan Abrahante ◽  
Yen-Yi Ho ◽  
Rachel Isaksson Vogel ◽  
...  
Keyword(s):  
Cancer Gene ◽  
Genetic Screens ◽  
Driver Genes ◽  
Cancer Driver ◽  
Forward Genetic Screens ◽  
Candidate Cancer Gene ◽  
Gene Database ◽  
Cancer Driver Genes

scholarly journals A STUDY ON THE HISTONE METHYLTRANSFERASE ENHANCER OF ZESTE HOMOLOG 2 EXPRESSION IN BREAST CARCINOMA

2020 ◽  
pp. 66-68
Author(s):  
Rubaiya Ahmad ◽  
Syed Meraj Imam ◽  
Debarshi Jana
Keyword(s):  
Breast Carcinoma ◽  
Breast Tumor ◽  
Triple Negative ◽  
Histone Methyltransferase ◽  
Expression Level ◽  
High Grade ◽  
Over Expression ◽  
Ezh2 Expression ◽  
Triple Negative Breast Carcinoma ◽  
Enhancer Of Zeste

The over expression of EZH2 in Breast Carcinoma. Compare EZH2 expression in different immunophenotypes of breast carcinoma(basal, luminal, triple-negative). The study EZH2 expression level in association to staging and grading of breast carcinoma Patients attending the Dept of Pathology, Sri Krishna Medical Collage Muzaffarpur, Bihar with epithelial breast tumor. We found that EZH2 in Breast Carcinoma was significantly associated with grade of the tumour. EZH2 was significantly associated with stage of the tumour. It was found that EZH2 was significantly correlated with ki67 in Breast Carcinoma patients. Triple negative Breast Carcinoma patient was significantly associated with high grade of EZH2 tumour.

scholarly journals A OBSERVATIONAL STUDY ON CYTOKERATIN 5/6 EXPRESSION IN BREAST CARCINOMA PATIENTS AND CORRELATED WITH HORMONAL STATUS.

2020 ◽  
pp. 63-65
Author(s):  
Rubaiya Ahmad ◽  
Syed Meraj Imam ◽  
Debarshi Jana
Keyword(s):  
Breast Carcinoma ◽  
Research Study ◽  
Triple Negative ◽  
High Grade ◽  
Breast Cancers ◽  
Genetic Characteristics ◽  
Triple Negative Breast Carcinoma ◽  
Cytokeratin 5 ◽  
Malignant Lesions ◽  
Diagnostic Modalities

INTRODUCTION Breast cancer is the second most common cause of morbidity and mortality worldwide in women. They vary remarkably in terms of clinical presentation, history, behaviour and genetic characteristics. There has been a significant increase in overall incidence of breast cancers especially so in the developing countries attributable mainly to globalization causing adaptation of western life style and improved access to diagnostic modalities. OBJECTIVE OF THE RESEARCH Study of cytokeratin 5/6 expression in proliferative, preinvasive and malignant lesions of breast. ER/PR expression in proliferative, preinvasive and malignant lesions of breast. Correlation of data using appropriate statistical methods. METHODOLOGY Patients attending the Dept of Pathology, Sri Krishna Medical Collage Muzaffarpur, Bihar with epithelial breast tumor. RESULT AND CONCLUSION We found that cytokeratin 5/6 expression in Breast Carcinoma was significantly associated with high grade of the tumour. cytokeratin 5/6 expression was significantly associated with advanced stage of the tumour. It was found that cytokeratin 5/6 expression was significantly correlated with ki67 in Breast Carcinoma patients. Hormonal receptor like ER and PR were was significantly associated with cytokeratin 5/6 expression tumour. Triple negative Breast Carcinoma patient was significantly associated with high grade of cytokeratin 5/6 expression tumour.

Higher CD1a Levels Correlate with PD-L1 Expression and Predict Worse Overall Survival in Triple-Negative Breast Carcinoma

Breast Care ◽  
2021 ◽  
pp. 1-9
Author(s):  
Jian Zheng ◽  
Yuntao Wei ◽  
Xiaoxi Li ◽  
Zhan Shen ◽  
Yong Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Dendritic Cells ◽  
Lymph Node ◽  
Breast Carcinoma ◽  
Triple Negative ◽  
Carcinoma Tissue ◽  
Kaplan Meier ◽  
Immature Dendritic Cells ◽  
Triple Negative Breast Carcinoma ◽  
High Median

Objective: The aim of this study was to measure the expression of PD-L1, CD1a (a marker for immature dendritic cells), and CD83 (a marker for mature dendritic cells) and further examine the associations of PD-L1, CD83, and CD1a with overall survival (OS) in triple-negative breast carcinoma patients. Methods: PD-L1, CD1a, and CD83 expression in breast carcinoma tissues and CD83 expression in lymph node tissues were examined by immunohistochemistry and tissue microarray in 159 patients. Patients were classified into the low, medium, and high PD-L1, CD1a, and CD83 levels. Pearson χ2 test was used to analyze the correlations between PD-L1, CD1a, and CD83. The Kaplan-Meier method was used to calculate the OS. Multivariate analysis was used to identify determinants of 3- and 5-year OS. Results: 25.1, 25.8, and 49.1% of the patients had low, medium, and high PD-L1 levels, respectively. PD-L1 levels significantly correlated with CD1a (r = 0.30409, p < 0.001) and CD83 levels (r = 0.6146, p < 0.001) in breast carcinoma tissue, as well as CD83 levels (r = 0.17508, p = 0.027) in lymph node. The median OS was 83 months (range 12–106), and the 3- and 5-year OS rates were 94.97% (95% CI 91.57–98.37) and 86.79% (95% CI 81.53–92.06), respectively. Moreover, patients with high median CD1a levels had a significantly lower 5-year OS rate (75.6%) than those with low median CD1a levels (93.5%, p = 0.038). Conclusion: PD-L1, CD1a, and CD83 are variably expressed in triple-negative breast carcinoma tissues, and PD-L1 expression correlates with CD1a and CD83. Higher CD1a levels correlate with PD-L1 expression and predict worse OS in triple-negative breast carcinoma.

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