Identification of recurrent genetic and epigenetic alterations of SALL3 in TNBC by comprehensive genomic analysis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07200
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: The University of Tokushima
• Principal Investigator: MATSUSHITA Yosuke 徳島大学, 先端酵素学研究所(プロテオ), 助教 (70634450)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: トリプルネガティブ乳癌

Outline of Final Research Achievements

Triple-negative breast cancers (TNBC) is a highly heterogeneous disease with problems of early recurrence and resistance to therapeutic agents. In this study, SALL3 showed frequent inactivation (frequent downregulation / mutation). By analyzing the molecular mechanism of TNBC, we attempted to identify new biological properties of TNBC. As a result, the frequent decrease in SALL3 expression is mainly regulated by promoter methylation, and this correlation is only controlled in TNBC. In addition, it was shown that SALL3 regulates the expression of its target gene by forming a transcription complex, and that the downregulation of SALL3 or target-gene contributes to resistance to paclitaxel or docetaxel.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

TNBCはERやHER2陽性サブタイプと異なり, 明確な治療標的が存在しないため, 内分泌療法や抗HER2療法の効果が期待できない. さらに, 概して予後が悪く, 早期再発も多いことから, TNBCの予後改善を目的とした治療法の確立, メカニズムの解明は急務であった. 高頻度に不活化 (発現低下・変異) を認めた SALL3の分子機構を解析することで, TNBCの新たな生物学的特徴付けは, 治療法確立に繋がることが期待されるため, 本研究の社会的意義は大きいと考えられる.