Genetic alteration in anaplastic transformation mechanism in same patients

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K16846
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: SUBAT Sophia 公益財団法人がん研究会, がん研究所 病理部, 研究員 (80774158)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 未分化癌 / 乳頭癌 / 濾胞型乳頭癌 / 次世代シークエンス / がんの進化

Outline of Final Research Achievements

In the current study, we performed next-generation sequencing of DNA from the extremely rare two case patients of concomitant PTC and ATC components, as well as one case of metachronous FVPTC and ATC components, along with their corresponding normal DNA. Our analysis of somatic mutations revealed a higher frequency of tumor mutational burdens in the concomitant cases with ATC components compared with PTC components. The ATC components also exhibited a large number of private driver mutations and more genetic alterations in oncogenic driver genes such as TP53. Yet, the phylogenetic trees represent a low number of shared trunk mutations, specifically BRAF and MAP3K1 mutations, respectively. However, interestingly, we observed a similar mutation incidence in the metachronous case of FVPTC components between ATC components. It is worth noting that the number of high-confidence somatic mutations was higher in the FVPTC than in the ATC component.

Free Research Field

甲状腺がん

Academic Significance and Societal Importance of the Research Achievements

甲状腺未分化癌は悪性度が極めて高く、症例数が少ないため、検体の入手が困難である。したかって、そもそも未分化癌自体の報告が少ない。さらに、同一患者内で未分化転化前後の検体が利用されるケースは極めて限られている。本研究では、初めて同一症例における乳頭癌・未分化癌の成分を用いて全ゲノムシークエンス、初めて同一症例における濾胞型乳頭癌と未分化癌成分を用いて全エクソームシークエンスを行なった研究である。同一患者における2つの異なる腫瘍成分の分岐進化起源を示すのに役たち、分化癌および未分化癌の関係について理解を深める可能性を与えると考えられる。