Analysis of cancer-specific mutations overlapping on phosphorylation motifs

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22569
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Kanazawa Medical University
• Principal Investigator: YOSHIZAKI Hisayoshi 金沢医科大学, 医学部, 講師 (00443490)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: リン酸化 / がん特異的変異

Outline of Final Research Achievements

Cancer cells acquire their phenotype through the accumulation of mutations that disrupt signaling pathways. Although the development of next-generation sequencing technologies has generated a vast amount of information on novel cancer cell mutations, most mutations, except for high-frequency mutations, are hidden behind passenger mutations that randomly enter due to genomic instability of cancer tissues, and are buried without being investigated for their contribution to oncogenesis and functional roles. This study proposed a method to comprehensively evaluate mutations that enter on phosphorylation signals, which have important roles in intracellular signaling.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本課題で開発した解析手法は、シグナル伝達経路のリワイヤリングを追跡できる。我々の解析手法は膨大な情報から自然選択された結果としての突然変異の意味を考えるきっかけを与え、未知のがんシグナル同定の一助になることが期待される。リン酸化モチーフ上の変異は集団で扱うため高頻度に見えるが、分子単位では、ほとんどが低頻度変異である。がん組織における低頻度遺伝子変異の不均一性は、個別化医療の必要性の根拠にもなっており 、個別化医療を進めるうえでもがん化に影響を持つ低頻度遺伝子変異の解析技術の開発は学術的意義が高い。