Aggressive prostate cancer with somatic loss of the homologous recombination repair gene FANCA: a case report

Abstract

Background: Precision medicine based on genomic analysis of germline or tumor tissue is attracting attention. However, there is no consensus on how to apply the results of genomic analysis to treatment. Case presentation: A 59-year-old man diagnosed with metastatic prostate cancer was diagnosed with castrationresistant prostate cancer. Although he was sequentially treated with enzalutamide and abiraterone, bone metastasis progression was identified by skeletal scintigraphy. Therefore, we sequentially performed docetaxel therapy followed by cabazitaxel. After the third cycle of cabazitaxel, his prostate-specific antigen level was stable at < 10 ng/mL, and no radiological progression was detected. The patient's formalin-fixed paraffin-embedded tumor biopsy specimen underwent multiple-gene testing by next-generation sequencing, which identified a FANCA homodeletion. No significant germline mutation was observed. Conclusions: We describe a case of aggressive, castration-resistant prostate cancer with FANCA homodeletion. Genomic analysis of prostate cancer tissue can be useful to determine optimal treatment of such cancers.

WITHDRAWN: A first Japanese Case of Intraductal Cancer of the Prostate with CHEK2 Mutation

“…We previously reported genomic analysis of tumor biopsy tissue of prostatic adenocarcinoma cases, which suggested FANCA and BRCA2 loss might be associated with tumor aggressiveness [6,7]. In this case, we investigated genomic feature of intraductal carcinoma of the prostate (IDC-P) and identi ed PTEN pathogenic mutations with LOH.…”

A Multiple Primary Malignancy Patient With FANCA Gene Mutation: A Case Report and Literature Review

“…Hierarchical clustering analysis showed that the DNA damage repair (DDR) pathways, especially the FA pathway, were deranged across all subtypes of GC (17). The association between FANCA gene variations and breast and ovarian cancers has also been confirmed (18,19), and the other cancers most reported to be associated with FANCA mutations are GC (17), prostate cancer (20) and colorectal cancer (21). There have been no reports on thyroid cancer yet.…”

Pulmonary metastasis secondary to abiraterone‐resistant prostate cancer with homozygous deletions of BRCA2: First Japanese case

“…Olaparib is a PARP inhibitor that has just been approved for patients with PCa and DDR mutations including BRCA2 loss 8,9 . In the future, PARP inhibitors may be the optimal treatment for PCa with BRCA2 gene alteration in Japan 10,11 …”

“…8,9 In the future, PARP inhibitors may be the optimal treatment for PCa with BRCA2 gene alteration in Japan. 10,11 There are various opinions concerning the relationship between BRCA alteration and responsiveness for treatment using ABI or enzalutamide. Annala et al 12 reported that patients with BRCA2 germline mutation exhibited poor responses to therapies that targeted the AR signaling axis, and in contrast, Antonarakis et al 13 reported a good response to AR targeting therapies.…”

“…Recently, we have reported several cases of somatic and germline mutations in DDR-related genes. 6,11 Collectively, these trials and case reports indicate that the ongoing examination of gene mutations may have a significant impact on future treatments for PCa in addition to the use of PARP inhibitors or platinum-based chemotherapy. Nonetheless, because PCa tends to be heterogeneous within each subtype, genetic testing should be used to develop more specific treatment strategies.…”