This issue contains four articles that make us think about the indications and methods of genetic analysis of tumors.
Matsumoto et al. reported on a 59-year-old patient with BRCA2 and RB1 co-loss organ-confined prostate cancer [1]. This cancer is usually detected at a more advanced stage and has a poor prognosis. Because their institution performs gene sequencing as a clinical study in all cases, they found this tumor was a highly malignant molecular subtype.
Hongo et al. reported a metastatic neuroendocrine prostate cancer in a 59-year-old man [2]. BRCA2 and AURKA mutations were detected in both biopsy tissue and cell-free DNA (cfDNA) of the tumor, demonstrating the utility of cfDNA analysis.
Uchida et al. reported a case of HER2-positive breast cancer in a 42-year-old germline BRCA1 gene large rearrangement carrier [3]. HER2-positive breast cancer in a BRCA1 mutation carrier is rare, and BRCA1 gene large rearrangement is an infrequent BRCA1 mutation that is not detected by conventional sequencing. This case suggests that different subtypes of breast cancer may arise depending on the type of BRCA1 mutation, and further study is needed.
Nishikubo et al. reported on a 28-year-old woman with colorectal carcinoma [4]. In this tumor, Lynch syndrome was suspected by immunohistochemistry. Genetic analysis revealed a mutation of unknown significance in the intron of MLH1. They then performed reverse transcription-PCR using mRNA extracted from the patient’s lymphocytes and found that there was an abnormal splicing of MLH1.
These four case reports reveal, by detailed analysis of the genes, new pathological conditions of tumors that were not discovered some time ago. Universal testing of tumors and cfDNA, using not only sequencing but also methods to detect large gene rearrangement and splicing abnormality, will open the way to precision medicine.
Footnotes
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References
- 1.Matsumoto K, Kosaka T, Nakamura K, et al. A first Japanese case of BRCA2 and RB1 co-loss organ-confined prostate cancer successfully treated by radical prostatectomy. Int Canc Conf J. 2021 doi: 10.1007/s13691-021-00469-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
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