Predicting drug response for basal cell carcinoma by comprehensive genomic analysis.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16898
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Kyushu University
• Principal Investigator: Akiyama Masato 九州大学, 医学研究院, 講師 (10757686)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: がんゲノム / 悪性腫瘍 / ゲノム医療 / 薬理遺伝学 / 次世代シークエンス

Outline of Final Research Achievements

We performed exome sequencing on blood and tumor samples from 24 cases of basal cell carcinoma (BCC) of the eyelid. In addition to the three known BCC-associated genes, we found a significant association of an novel gene, even after multiple testing corrections. The non-synonymous somatic mutations in the newly identified gene were detected in 12 samples (50%). Of these, nine were loss-of-function mutations. The somatic mutations in genes belonging to the Hedgehog signaling pathway were detected in 18 samples (67%), suggesting their significance as major genes in BCC of the eyelid. Although some mutations in SMO gene were known to affect responsiveness to vismodegib, the detected mutations in the present study had not been reported to be associated with response to vismodegib.

Free Research Field

眼腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究は、日本人の眼瞼部基底細胞癌を対象とした初の網羅的ゲノム解析である。主要ながん遺伝子は、1) 近年、眼部に発生する悪性腫瘍は同一の組織型であっても体細胞変異プロファイルが異なることが報告されているが、過去の眼瞼部に限定しない研究と類似していること、2) 海外から報告された結果と類似していることを示した一方で、過去に報告のない一つの遺伝子の関連を明らかにした。また、対象者数は少ないものの、vismodegibに抵抗性が知られている変異は本研究では同定されないことを確認した。