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.