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Long-term survival of an ovarian cancer patient harboring a RAD51C missense mutation.

ABSTRACT: Mutations in homologous recombination (HR) genes predispose to cancer but also sensitize to chemotherapeutics. Although therapy can initially be effective, cancers frequently cease responding, leading to recurrence and poor prognosis. Here we identify a germline mutation in RAD51C, a critical HR factor and known tumor suppressor, in an ovarian cancer patient with exceptionally long, progression-free survival. The RAD51C-T132P mutation is in a highly conserved residue within the nucleotide-binding site and interferes with single-strand DNA binding of the RAD51 paralog complex RAD51B-RAD51C-RAD51D-XRCC2 and association with another RAD51 paralog XRCC3. These biochemical defects lead to highly defective HR and drug sensitivity in tumor cells, ascribing RAD51C-T132P as a deleterious mutation that was likely causal for tumor formation. Conversely, its position within a critical site suggests that it is refractory to secondary mutations that would restore RAD51C gene function and lead to therapy resistance. A need for a greater understanding of the relationship between mutation position and reversion potential of HR genes is underscored, as it may help predict the effectiveness of therapies in patients with HR-deficient cancers.

SUBMITTER: Sullivan MR

PROVIDER: S-EPMC8040731 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Long-term survival of an ovarian cancer patient harboring a RAD51C missense mutation.

Sullivan Meghan R MR Prakash Rohit R Rawal Yashpal Y Wang Weibin W Sung Patrick P Radke Marc R MR Kaufmann Scott H SH Swisher Elizabeth M EM Bernstein Kara A KA Jasin Maria M

Cold Spring Harbor molecular case studies 20210408 2

Mutations in homologous recombination (HR) genes predispose to cancer but also sensitize to chemotherapeutics. Although therapy can initially be effective, cancers frequently cease responding, leading to recurrence and poor prognosis. Here we identify a germline mutation in <i>RAD51C</i>, a critical HR factor and known tumor suppressor, in an ovarian cancer patient with exceptionally long, progression-free survival. The RAD51C-T132P mutation is in a highly conserved residue within the nucleotide ...[more]

PMID: 33832919

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Project description:Ovarian cancer patients with BRCA1 mutation have more susceptibility for secondary breast cancer. In females with BRCA1 mutation, the risk of developing breast carcinoma is 65% and of ovarian cancer is 39%, before 70 years of age. This is a case report of a 74 year old, post-menopausal woman diagnosed with metastatic retroperitoneal lymph node, high-grade papillary adenocarcinoma primary ovary stage IIIA in April 2004 at the age of 48 years. She underwent 3 cycles of neo-adjuvant chemotherapy Inj. Methotrexate and Inj. Carboplatin from June to August 2004 followed by optimum cytoreduction in September 2004. Later she completed 3 more cycles of chemotherapy of the same protocol from October to November 2004. Tab Etoposide was given from December 2004 to October 2006. In May 2006, during oral chemotherapy and with unremarkable radiological findings, the patient chose Ayurvedic treatment in view of immune boosting, and improving quality of life. The patient underwent 11 sets of Panchakarma treatment, almost every year, from December 2007 to September 2019. She was disease-free for 13 years leading a good quality of life with adjunct Ayurvedic treatment. In October 2019, she was diagnosed with Left breast duct carcinoma with ER, PR hormone positive status. Her genetic mutation analysis report at that time revealed BRCA 1 mutation. She underwent Left Modified Radical Mastectomy in October 2019, followed by prophylactic Right Breast Mastectomy and oral hormonal therapy. Now she is living with better quality of life with adjunct Ayurvedic treatment, including Oral Ayurvedic Medicines possessing Rasayana (immunomodulatory) and hepato-protective activity and 12 sets of Panchakarma Chikitsa. In this case of Stage IIIA Ovarian carcinoma and second primary Breast carcinoma with BRCA 1 genetic mutation (HBOC syndrome), a long-term 13 years of disease-free survival, and 20 years of overall survival is achieved with the integration of Ayurvedic treatment and conventional cancer treatment.

Dataset Information

Long-term survival of an ovarian cancer patient harboring a RAD51C missense mutation.

Publications

Long-term survival of an ovarian cancer patient harboring a RAD51C missense mutation.

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