Somatic Mutational Profile of High-Grade Serous Ovarian Carcinoma and Triple-Negative Breast Carcinoma in Young and Elderly Patients: Similarities and Divergences
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 TN...
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2021-12-01
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| author | Pedro Adolpho de Menezes Pacheco Serio Gláucia Fernanda de Lima Pereira Maria Lucia Hirata Katayama Rosimeire Aparecida Roela Simone Maistro Maria Aparecida Azevedo Koike Folgueira |
| author_facet | Pedro Adolpho de Menezes Pacheco Serio Gláucia Fernanda de Lima Pereira Maria Lucia Hirata Katayama Rosimeire Aparecida Roela Simone Maistro Maria Aparecida Azevedo Koike Folgueira |
| author_sort | Pedro Adolpho de Menezes Pacheco Serio |
| collection | DOAJ |
| description | 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 <i>TP53</i>, which was mutated in 67–83% of the samples, the affected TSG in <i>TP53</i> wild-type samples were <i>NF1</i> (yHGSOC and yTNBC), <i>PHF6</i> (eHGSOC and yTNBC), <i>PTEN</i>, <i>PIK3R1</i> and <i>ZHFX3</i> (yTNBC), <i>KMT2C</i>, <i>ARID1B</i>, <i>TBX3,</i> and <i>ATM</i> (eTNBC). A few samples only presented one affected oncogene (but no TSG): <i>KRAS</i> and <i>TSHR</i> in eHGSOC and <i>RAC1</i> and <i>PREX2</i> (a regulator of <i>RAC1</i>) 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. |
| first_indexed | 2024-03-10T04:25:10Z |
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| language | English |
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| spelling | doaj.art-c5daed62b79d41cfb949c8d9cd8c77b02023-11-23T07:39:51ZengMDPI AGCells2073-44092021-12-011012358610.3390/cells10123586Somatic Mutational Profile of High-Grade Serous Ovarian Carcinoma and Triple-Negative Breast Carcinoma in Young and Elderly Patients: Similarities and DivergencesPedro Adolpho de Menezes Pacheco Serio0Gláucia Fernanda de Lima Pereira1Maria Lucia Hirata Katayama2Rosimeire Aparecida Roela3Simone Maistro4Maria Aparecida Azevedo Koike Folgueira5Centro de Investigação Translacional em Oncologia, Departamento de Radiologia e Oncologia, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246-000, BrazilCentro de Investigação Translacional em Oncologia, Departamento de Radiologia e Oncologia, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246-000, BrazilCentro de Investigação Translacional em Oncologia, Departamento de Radiologia e Oncologia, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246-000, BrazilCentro de Investigação Translacional em Oncologia, Departamento de Radiologia e Oncologia, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246-000, BrazilCentro de Investigação Translacional em Oncologia, Departamento de Radiologia e Oncologia, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246-000, BrazilCentro de Investigação Translacional em Oncologia, Departamento de Radiologia e Oncologia, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246-000, BrazilBackground: 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 <i>TP53</i>, which was mutated in 67–83% of the samples, the affected TSG in <i>TP53</i> wild-type samples were <i>NF1</i> (yHGSOC and yTNBC), <i>PHF6</i> (eHGSOC and yTNBC), <i>PTEN</i>, <i>PIK3R1</i> and <i>ZHFX3</i> (yTNBC), <i>KMT2C</i>, <i>ARID1B</i>, <i>TBX3,</i> and <i>ATM</i> (eTNBC). A few samples only presented one affected oncogene (but no TSG): <i>KRAS</i> and <i>TSHR</i> in eHGSOC and <i>RAC1</i> and <i>PREX2</i> (a regulator of <i>RAC1</i>) 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.https://www.mdpi.com/2073-4409/10/12/3586triple-negative breast cancerhigh-grade serous ovarian carcinomasomaticyoung adult |
| spellingShingle | Pedro Adolpho de Menezes Pacheco Serio Gláucia Fernanda de Lima Pereira Maria Lucia Hirata Katayama Rosimeire Aparecida Roela Simone Maistro Maria Aparecida Azevedo Koike Folgueira Somatic Mutational Profile of High-Grade Serous Ovarian Carcinoma and Triple-Negative Breast Carcinoma in Young and Elderly Patients: Similarities and Divergences Cells triple-negative breast cancer high-grade serous ovarian carcinoma somatic young adult |
| title | Somatic Mutational Profile of High-Grade Serous Ovarian Carcinoma and Triple-Negative Breast Carcinoma in Young and Elderly Patients: Similarities and Divergences |
| title_full | Somatic Mutational Profile of High-Grade Serous Ovarian Carcinoma and Triple-Negative Breast Carcinoma in Young and Elderly Patients: Similarities and Divergences |
| title_fullStr | Somatic Mutational Profile of High-Grade Serous Ovarian Carcinoma and Triple-Negative Breast Carcinoma in Young and Elderly Patients: Similarities and Divergences |
| title_full_unstemmed | Somatic Mutational Profile of High-Grade Serous Ovarian Carcinoma and Triple-Negative Breast Carcinoma in Young and Elderly Patients: Similarities and Divergences |
| title_short | Somatic Mutational Profile of High-Grade Serous Ovarian Carcinoma and Triple-Negative Breast Carcinoma in Young and Elderly Patients: Similarities and Divergences |
| title_sort | somatic mutational profile of high grade serous ovarian carcinoma and triple negative breast carcinoma in young and elderly patients similarities and divergences |
| topic | triple-negative breast cancer high-grade serous ovarian carcinoma somatic young adult |
| url | https://www.mdpi.com/2073-4409/10/12/3586 |
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