Case Report: A Pancreatic Ductal Adenocarcinoma Patient With Concurrent Targetable Somatic Novel KANK1-ALK, UPP2-NTRK3 Fusion, and Pathogenetic Germline BRCA Mutation

Pancreatic ductal adenocarcinoma (PDAC) is presently one of the cancers with the worst survival rates. The current treatment options for PDAC are relatively scarce due to insufficient understanding of molecular characteristics and subtypes of PDAC. Based on next-generation sequencing (NGS), we firstly presented a case about a KRAS wild-type pancreatic ductal adenocarcinoma patient harboring a concurrent targetable rare somatic novel KANK1-ALK, UPP2-NTRK3 fusion, and pathogenetic germline BRCA mutation. These two novel fusion statuses were assayed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). Our findings demonstrated that comprehensive and systematic screening of PDAC for actionable genomic alteration may substantially improve the therapeutic prospects for a sizeable fraction of patients with PDAC. To improve the management of PDAC in an era of precision medicine, it is important to identify ALK or NTRK fusion-positive and pathogenic germline mutation subsets of patients who can benefit from targeted therapies.

Differences in Ovarian and Other Cancers Risks by Population and BRCA Mutation Location

Hereditary breast and ovarian cancer is caused by a germline mutation in BRCA1 or BRCA2 genes. The frequency of germline BRCA1/2 gene mutation carriers and the ratio of germline BRCA1 to BRCA2 mutations in BRCA-related cancer patients vary depending on the population. Genotype and phenotype correlations have been reported in BRCA mutant families, however, the correlations are rarely used for individual risk assessment and management. BRCA genetic testing has become a companion diagnostic for PARP inhibitors, and the number of families with germline BRCA mutation identified is growing rapidly. Therefore, it is expected that analysis of the risk of developing cancer will be possible in a large number of BRCA mutant carriers, and there is a possibility that personal and precision medicine for the carriers with specific common founder mutations will be realized. In this review, we investigated the association of ovarian cancer risk and BRCA mutation location, and differences of other BRCA-related cancer risks by BRCA1/2 mutation, and furthermore, we discussed the difference in the prevalence of germline BRCA mutation in ovarian cancer patients. As a result, although there are various discussions, there appear to be differences in ovarian cancer risk by population and BRCA mutation location. If it becomes possible to estimate the risk of developing BRCA-related cancer for each BRCA mutation type, the age at risk-reducing salpingo-oophorectomy can be determined individually. The decision would bring great benefits to young women with germline BRCA mutations.