Genomic Analysis:
Although the previously resected metastatic left frontal subcutaneous SCC was deemed unsuitable due to the lack of tumor invasion there, the combined positive score (CPS) was checked using PD-L1 IHC 22C3 pharmDx and the result was negative (<1). The same sample was also subjected to next-generation sequencing using OncoGuideâ„¢ NCC Oncopanel System version 2.01, which was designed to examine somatic and germline mutations and copy number alterations within the entire coding region of 124 genes, fusions of 12 oncogenes, tumor mutational burden (TMB), and microsatellite instability (MSI). Next-generation sequencing revealed multiple genomic alterations (AXL, ERBB2, NOTCH2, ROS1, and TSC1), all of which are rare genetic polymorphisms but not oncogenetically important. The TMB, which includes all mutations, including synonymous mutations, within the entire targeted region was low at 2.30 mutations per megabase. High-level microsatellite instability (MSI-H) which is a form of genetic instability caused by mismatch repair deficiency, was not detected. In conclusion, next-generation sequencing did not detect genetic abnormalities which related to the predictive value of drug effectiveness.
It was difficult to identify the type of XP in this case. In Japan, 55% of patients with XP-A, which leads to severe cutaneous and neurological symptoms, followed by XP-V, which leads only to cutaneous symptoms [7-9]. Our patient had no neurological symptoms, so a genetic test for POLH was performed on the suspicion that he with XP-V, but the result was negative. In Japan, genetic testing for XP is covered by health insurance but only for one causative gene. Therefore, after obtaining approval from the institutional review board of Kobe University and securing informed consent, we measured the patient’s UDS (unscheduled DNA synthesis) ability, using a previously described method [11]. Fibroblasts cultured from an intact skin specimen from his medial side of left upper arm were compared with those from a 2-year-old patient with XP-A (XP173KO) and those from a healthy 27-year-old control. His UDS was found to have decreased to 19% that of the healthy control [Figure 2]. He was diagnosed with XP based on his clinical symptoms and the decrease in UDS. However, his XP subtype could not be identified.