Genomic profiling with whole‐exome sequencing revealed distinct mutations and novel pathways in Asian melanoma

Abstract

Cutaneous melanoma (CM) is a cancer that develops from melanocytes, involving the epidermis-dermis junction and then invading the dermis and subcutaneous tissue. 1 Melanoma is a potentially fatal cancer and is one of the most common malignancies in terms of years of life lost per death. 2 The incidence of invasive melanoma has risen rapidly in recent decades. 1 Globally, the highest incidence of melanoma is reported in Australia and New Zealand, but the rates are significantly lower in Asia and Africa. 2 In Caucasians, the disease most often occurs on the back of male patients and on the legs of female patients. 3 In contrast, a significant proportion of Asian melanomas occur on the palms and soles. 4 The variation in body site-specific incidence among the different regions of the world seems to be correlated with sun exposure and the photoprotective role of skin pigmentation. 2,5,6 UV radiation is known to

Comparative transcriptomic analysis reveals differences in gene expression and regulatory pathways between nonacral and acral melanoma in Asian individuals

“…In our previous study, although we identified mutational signature 12 as the predominant variant, we observed significant differences between AM and NAM in terms of certain mutational signatures, such as in mutational signatures 7, 21, and 22. 15 We also discovered that NAM samples exhibited significantly high concentrations of mutational signatures 7, 21, and 22 along with increased TMB and microsatellite instability (MSI). 15 In this study, after the analysis of various DNA sequences, we used transcriptome sequencing to examine the differences in RNA expression between AM and NAM.…”

“…15 We also discovered that NAM samples exhibited significantly high concentrations of mutational signatures 7, 21, and 22 along with increased TMB and microsatellite instability (MSI). 15 In this study, after the analysis of various DNA sequences, we used transcriptome sequencing to examine the differences in RNA expression between AM and NAM.…”

“…[12][13][14] In our previous study, which is regarded as the first whole-exome sequencing (WES) study to be conducted in Asian individuals, we investigated the differences in the genomic profiles of melanoma between Asian and White individuals. 15 We discovered that in Taiwanese patients, mutational signature 12 was the predominant variant, accounting for approximately 45% of the observed mutational signatures. By contrast, according to The Cancer Genome Atlas (TCGA), mutational signature 7 (UV mutational signature) is the predominant variant in White patients.…”

“…16 In addition, our previous study revealed a significantly lower tumor mutation burden (TMB) in our cohort compared with that in White individuals. 15 In Asian individuals with melanoma, reduced UV signature and TMB may contribute to a lower BRAF mutation rate and a lower response rate to immunotherapy. 17,18 Therefore, further research is required to address these challenges and improve the outcomes of melanoma in Asia.…”

Diagnostic value of 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography imaging in acral melanoma–predominant Asian patients

“…In contrast, it is the predominant subtype in non-Caucasian societies; it is also distinct because it has a different pathogenesis and genetic background and is less often related to excess ultraviolet exposure. [16][17][18][19] To the best of our knowledge, there is only one study reported the staging function of PET/CT in Japanese with acral melanoma (by Ide et al 20 ). However, the study exclude any clinical signs of distal metastasis and most of them (100 over 109) did not have clinical palpable nodes.…”