<i>BRCA1</i> Reversion Mutation Confers Resistance to Olaparib and Camrelizumab in a Patient with Breast Cancer Liver Metastasis

Pan, Jiaxing; Lei, Lei; Ye, Wei-Wu; Wang, Xiao-Jia; Cao, Wen

doi:10.4048/jbc.2021.24.e39

Cited by 6 publications

(6 citation statements)

References 16 publications

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“…BRCA1 gene exon deletions have been reported before in HBOC cases [15,16]. Moreover, Pan et al, have reported BRCA1 gene exon 7-8 deletion, in hereditary ovarian cancer cases [17].…”

Section: Discussionmentioning

confidence: 92%

BRCA1/2 variants and copy number alterations status in non familial triple negative breast cancer and high grade serous ovarian cancer

Ansari

Jouali²,

Fekkak³

et al. 2022

Hered Cancer Clin Pract

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Background While the role of BRCA1/2 genes in familial breast and ovarian cancer is well established, their implication in the sporadic form of both cancers is still controversial. With the development of poly (ADP-ribose) polymerase (PARP) inhibitors, the exact relationship between BRCA1/2 genes and sporadic triple negative breast cancer/high grade serous carcinoma (TNBC/HGSC) needs to be further investigated. Therefore, we conducted a study in which we analyze BRCA1/2 point mutations and copy number alterations in Moroccan patients suffering from TNBC/HGSC. Methods To achieve our goal, we analyzed BRCA1/2 genes in the FFPE tissue blocks and blood samples of 65 TNBC/HGSC selected patients, using next generation sequencing technology. Results From the 65 successfully sequenced patients in our cohort, we detected five-point variants in six different patients, four variants were classified as pathogenic and one of unknown significance. Regarding copy number alterations we detected one copy number loss in BRCA1 gene and one copy number gain in BRCA2 gene. The genetic screening of BRCA1/2 genes using these patients’ genomic DNA indicated that five harbored a germline genetic alteration. While three harbored a somatic genetic alteration. To the best of our knowledge, three-point variants detected in our study have never been reported before. Conclusion According to the results found in the present study, in a population without a family history of cancer, the possibility of a BRCA1/2 somatic pathogenic variant in high grade serous carcinoma is 7%. While for Triple negative breast cancer somatic point variants and copy number alterations seems to be a very rare genetic event.

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“…BRCA1 gene exon deletions have been reported before in HBOC cases [15,16]. Moreover, Pan et al, have reported BRCA1 gene exon 7-8 deletion, in hereditary ovarian cancer cases [17].…”

Section: Discussionmentioning

confidence: 92%

BRCA1/2 variants and copy number alterations status in non familial triple negative breast cancer and high grade serous ovarian cancer

Ansari

Jouali²,

Fekkak³

et al. 2022

Hered Cancer Clin Pract

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“…Sequence analysis revealed that this mutation rearranged the reading frame of BRCA1 , and the researchers concluded that this unique BRCA1 revertant mutation was associated with drug resistance. 112 In addition, Xu et al. have reported a case of a BCLM patient with a phosphatase and tensin homolog deleted on chromosome ten ( PTEN ) mutation detected in liver metastatic tissue, and this mutation might have led to resistance to the PI3K inhibitor alpelisib (BYL719) in the patient.…”

Section: Factors Contributing To Drug Resistance In Bclmmentioning

confidence: 99%

Mechanisms of drug resistance in breast cancer liver metastases: Dilemmas and opportunities

Yan¹,

Zhao²,

Wei³

et al. 2023

Molecular Therapy - Oncolytics

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“…3 Importantly, reversion mutation has been recently reported as a mechanism of resistance to the PARP inhibitor olaparib. 5,6 Herein, we describe a case of a patient with breast cancer with aBRCA2 pathogenic variant that was resistant to olaparib and was suspected to be a reversion mutation based on cancer genomic profiling.…”

Section: Introductionmentioning

confidence: 99%

BRCA2 reversion mutation confers resistance to olaparib in breast cancer

Yamamoto

KAWASHIMA

Fujiwara

et al. 2023

Preprint

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BRCA1 Reversion Mutation Confers Resistance to Olaparib and Camrelizumab in a Patient with Breast Cancer Liver Metastasis

Cited by 6 publications

References 16 publications

BRCA1/2 variants and copy number alterations status in non familial triple negative breast cancer and high grade serous ovarian cancer

BRCA1/2 variants and copy number alterations status in non familial triple negative breast cancer and high grade serous ovarian cancer

Mechanisms of drug resistance in breast cancer liver metastases: Dilemmas and opportunities

BRCA2 reversion mutation confers resistance to olaparib in breast cancer

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