Defects in homologous recombination repair genes are associated with good prognosis and clinical sensitivity to DNA-damaging agents in pancreatic cancer: A case report

Sonnenblick,Amir; Zick,Aviad; Maoz,Myriam; Cohen,Sherri; Kadouri,Luna; Peretz,Tamar; Hubert,Ayala

doi:10.3892/mco.2018.1588

Defects in homologous recombination repair genes are associated with good prognosis and clinical sensitivity to DNA-damaging agents in pancreatic cancer: A case report

Authors:
- Amir Sonnenblick
- Aviad Zick
- Myriam Maoz
- Sherri Cohen
- Luna Kadouri
- Tamar Peretz
- Ayala Hubert
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Affiliations: Sharett Institute of Oncology, Hadassah‑Hebrew University Medical Center, Ein Kerem, Jerusalem 91120, Israel
Published online on: March 9, 2018 https://doi.org/10.3892/mco.2018.1588
Pages: 683-685

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Abstract

Tumor genome sequencing is important for increasing our understanding of the development of cancer, which may be affected by different therapies. In the present study, genomic evolution was investigated in a patient with stage IV pancreatic cancer bearing a germline breast cancer 2 (BRCA2) mutation. The patient received cisplatin, a DNA cross-linking agent, which led to a long‑lasting complete response. Eventually the patient developed brain metastasis, suggesting the acquisition of resistance to cisplatin. He subsequently underwent brain lesion resection, radiofrequency ablation and chemotherapy, again resulting in long‑lasting response. Samples of blood, pancreatic tumor tissue and brain metastases were collected and the extracted DNA was sequenced. The pancreatic and brain lesions, when compared with the blood samples, exhibited mutations in the BRCA1 and checkpoint kinase 2 genes, in addition to the germline BRCA2 mutation. The brain lesion, when compared with the primary tumor, harbored no additional mutations or copy‑number variations. These findings suggest that the isolated relapse in the brain was due to pharmacological sanctuary rather than genomic alterations. It may be suggested that the presence of defects in the homologous recombination repair pathways are associated with a good prognosis and clinical sensitivity to agents that damage the DNA in pancreatic cancer.

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