Metastatic lung adenocarcinoma with BRCA2 mutation and longstanding disease control on olaparib, developing triple negative breast adenocarcinoma with additional BRCA2 reversion mutation: a case report
Abstract Background The BRCA2 gene is a well-known tumor suppressor gene implicated in breast and ovarian cancers. BRCA1/2 mutations can be sensitive to poly ADP-ribose polymerase (PARP) inhibitors such as olaparib. However, some of these patients develop resistance to this treatment and an essentia...
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Journal of Medical Case Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13256-023-04139-x |
| _version_ | 1797559454582964224 |
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| author | Auro del Giglio Beatriz da Costa Aguiar Alves André Márcio Murad Fernando Luiz Affonso Fonseca |
| author_facet | Auro del Giglio Beatriz da Costa Aguiar Alves André Márcio Murad Fernando Luiz Affonso Fonseca |
| author_sort | Auro del Giglio |
| collection | DOAJ |
| description | Abstract Background The BRCA2 gene is a well-known tumor suppressor gene implicated in breast and ovarian cancers. BRCA1/2 mutations can be sensitive to poly ADP-ribose polymerase (PARP) inhibitors such as olaparib. However, some of these patients develop resistance to this treatment and an essential factor contributing to acquired insensitivity is the occurrence of reversion mutations in the BRCA1/2 genes. Case presentation We report the case of a 65-year-old Brazilian female patient who had previously been diagnosed with metastatic lung carcinoma carrying a BRCA2 mutation that had extended to the central nervous system. Following disease progression, olaparib was administered, resulting in a stabilizing effect on her condition for ~ 30 months. During a routine follow-up, a new triple-negative breast tumor was found. Genetic testing revealed the presence of two distinct BRCA2 gene mutations in the breast tumor. The original mutation (p.Val220Ilefs4) led to a frameshift, culminating in the production of a truncated and non-functional BRCA2 protein; the second mutation, K437fs22, rectified the reading frame of exon 11. Consequently, Rad51 could properly bind to BRCA2—an essential protein crucial for DNA repair. This restoration resulted in a functional BRCA2 protein, effectively elucidating the clinical resistance observed in the new breast tumor in this case. Conclusions This case report highlights the clinical significance of comprehensive next-generation sequencing analyses for lung adenocarcinomas, both at diagnosis and upon progression. Such analyses enable informed decisions regarding targeted therapies and facilitate a deeper comprehension of resistance mechanisms. |
| first_indexed | 2024-03-10T17:45:41Z |
| format | Article |
| id | doaj.art-245731edf7c244e2a9b39f524c011904 |
| institution | Directory Open Access Journal |
| issn | 1752-1947 |
| language | English |
| last_indexed | 2024-03-10T17:45:41Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Medical Case Reports |
| spelling | doaj.art-245731edf7c244e2a9b39f524c0119042023-11-20T09:32:12ZengBMCJournal of Medical Case Reports1752-19472023-09-011711510.1186/s13256-023-04139-xMetastatic lung adenocarcinoma with BRCA2 mutation and longstanding disease control on olaparib, developing triple negative breast adenocarcinoma with additional BRCA2 reversion mutation: a case reportAuro del Giglio0Beatriz da Costa Aguiar Alves1André Márcio Murad2Fernando Luiz Affonso Fonseca3Departamento de Oncologia e Hematologia, Centro Universitário FMABCLaboratório de Análises Clínicas, Centro Universitário FMABCCENANTRON-PERSONAL-Precision OncologyLaboratório de Análises Clínicas, Centro Universitário FMABCAbstract Background The BRCA2 gene is a well-known tumor suppressor gene implicated in breast and ovarian cancers. BRCA1/2 mutations can be sensitive to poly ADP-ribose polymerase (PARP) inhibitors such as olaparib. However, some of these patients develop resistance to this treatment and an essential factor contributing to acquired insensitivity is the occurrence of reversion mutations in the BRCA1/2 genes. Case presentation We report the case of a 65-year-old Brazilian female patient who had previously been diagnosed with metastatic lung carcinoma carrying a BRCA2 mutation that had extended to the central nervous system. Following disease progression, olaparib was administered, resulting in a stabilizing effect on her condition for ~ 30 months. During a routine follow-up, a new triple-negative breast tumor was found. Genetic testing revealed the presence of two distinct BRCA2 gene mutations in the breast tumor. The original mutation (p.Val220Ilefs4) led to a frameshift, culminating in the production of a truncated and non-functional BRCA2 protein; the second mutation, K437fs22, rectified the reading frame of exon 11. Consequently, Rad51 could properly bind to BRCA2—an essential protein crucial for DNA repair. This restoration resulted in a functional BRCA2 protein, effectively elucidating the clinical resistance observed in the new breast tumor in this case. Conclusions This case report highlights the clinical significance of comprehensive next-generation sequencing analyses for lung adenocarcinomas, both at diagnosis and upon progression. Such analyses enable informed decisions regarding targeted therapies and facilitate a deeper comprehension of resistance mechanisms.https://doi.org/10.1186/s13256-023-04139-xBRCA2Reversion mutationTherapy resistance |
| spellingShingle | Auro del Giglio Beatriz da Costa Aguiar Alves André Márcio Murad Fernando Luiz Affonso Fonseca Metastatic lung adenocarcinoma with BRCA2 mutation and longstanding disease control on olaparib, developing triple negative breast adenocarcinoma with additional BRCA2 reversion mutation: a case report Journal of Medical Case Reports BRCA2 Reversion mutation Therapy resistance |
| title | Metastatic lung adenocarcinoma with BRCA2 mutation and longstanding disease control on olaparib, developing triple negative breast adenocarcinoma with additional BRCA2 reversion mutation: a case report |
| title_full | Metastatic lung adenocarcinoma with BRCA2 mutation and longstanding disease control on olaparib, developing triple negative breast adenocarcinoma with additional BRCA2 reversion mutation: a case report |
| title_fullStr | Metastatic lung adenocarcinoma with BRCA2 mutation and longstanding disease control on olaparib, developing triple negative breast adenocarcinoma with additional BRCA2 reversion mutation: a case report |
| title_full_unstemmed | Metastatic lung adenocarcinoma with BRCA2 mutation and longstanding disease control on olaparib, developing triple negative breast adenocarcinoma with additional BRCA2 reversion mutation: a case report |
| title_short | Metastatic lung adenocarcinoma with BRCA2 mutation and longstanding disease control on olaparib, developing triple negative breast adenocarcinoma with additional BRCA2 reversion mutation: a case report |
| title_sort | metastatic lung adenocarcinoma with brca2 mutation and longstanding disease control on olaparib developing triple negative breast adenocarcinoma with additional brca2 reversion mutation a case report |
| topic | BRCA2 Reversion mutation Therapy resistance |
| url | https://doi.org/10.1186/s13256-023-04139-x |
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