Mechanism of pathogenesis and therapy development using tumor suppressor gene Pten abnormal Cowden syndrome iPS cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11687
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Hiroshima University
• Principal Investigator: KANDA TAKU 広島大学, 病院(歯), 助教 (00423369)
• Co-Investigator(Kenkyū-buntansha): 岡本 哲治 広島大学, 医歯薬保健学研究科(歯), 教授 (00169153)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: COWDEN / PTEN / がん抑制遺伝子 / IPS / 無血清

Outline of Final Research Achievements

The peripheral blood of the cancer supressor gene Pten abnormal Cowden syndrome patient was searched for all exons of 4813 genes by MiSeq next generation sequencer. Deletion of T and c. 1027 G > A mutation were recognized in the allele of the PTEN gene region. These results suggest that the PTEN protein is truncated because the 341 amino acid F is replaced by L and the 342 amino acid K is replaced by R, followed by the formation of stop codon. After primary culture of PBMCs from the same patient, who also had mutations in cancer-related genes and had a history of breast cancer or thyroid cancer in this patient, in RD6F serum-free medium, disease-specific iPSCs were induced in a non-feeder serum-free culture system.

Free Research Field

外科系歯学

Academic Significance and Societal Importance of the Research Achievements

Cowden症候群は全身諸臓器の多発性過誤腫と高率に悪性腫瘍を合併する疾患で,がん抑制遺伝子phosphatase and tensin homolog deleted on chromosome 10 (PTEN)の変異が関与するまれな常染色体優性遺伝である。Cowden症候群特異的iPSCは、本疾患の病態解明及び治療法の開発研究おいて有用な手法と考えられる。