Department of Medical Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Department of Research and Development, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China.
BMC Med Genomics. 2021 Jan 6;14(1):6. doi: 10.1186/s12920-020-00850-6.
In addition to ovarian and breast cancers, loss-of-function mutations in BRCA1 and BRCA2 genes are also linked to an increased risk of pancreatic cancer, with ~ 4 to 7% of pancreatic cancer patients harboring germline BRCA mutations. Most BRCA alterations in pancreatic cancer are frame-shifting indels, stop-gain, and splice-site mutations, but single nucleotide substitutions are rare. Recent studies demonstrated a significant progression-free survival (PFS) benefit from maintenance olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor administered to patients with germline BRCA mutations and metastatic pancreatic cancer.
Here, we report a metastatic pancreatic cancer case who harbored a novel somatic BRCA2 c.6944T > C (p. I2315T) point mutation. After 6 weeks first-line chemotherapy, the patient was refractory to treatment and had a progressive disease. Due to the novel nonsynonymous BRCA2 point mutation, we decided to change the strategy by administering olaparib. The patient benefited from olaparib therapy and achieved a PFS of ~ 6.5 months.
We describe a patient carrying a novel somatic BRCA2 p. I2315T point mutation, which is first reported in metastatic pancreatic cancer. This case report indicates that a gene mutation-based strategy should be considered in the clinic to provide more effective treatment.
除了卵巢癌和乳腺癌，BRCA1 和 BRCA2 基因的功能丧失突变也与胰腺癌风险增加相关，约有 4%至 7%的胰腺癌患者携带种系 BRCA 突变。大多数胰腺癌中的 BRCA 改变是移码缺失、无义突变和剪接位点突变，但单核苷酸取代很罕见。最近的研究表明，对于携带种系 BRCA 突变和转移性胰腺癌的患者，使用多聚（ADP-核糖）聚合酶（PARP）抑制剂奥拉帕利进行维持治疗可显著改善无进展生存期（PFS）。
在这里，我们报告了一例携带新型体细胞 BRCA2 c.6944T > C（p. I2315T）点突变的转移性胰腺癌病例。一线化疗 6 周后，患者对治疗产生耐药性，疾病进展。由于新型非同义 BRCA2 点突变，我们决定通过奥拉帕利改变治疗策略。患者从奥拉帕利治疗中获益，无进展生存期约为 6.5 个月。
我们描述了一名携带新型体细胞 BRCA2 p. I2315T 点突变的患者，该突变首先在转移性胰腺癌中报道。该病例报告表明，基于基因突变的策略应在临床上考虑，以提供更有效的治疗。
