Multiregion analysis for early colorectal tumor

• Project/Area Number: 16K19107
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Kyushu University
• Principal Investigator: Saito Tomoko 九州大学, 大学病院, 医員 (10734741)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 早期大腸がん / 大腸線腫 / 全エキソームシーケンス / 腫瘍内不均一性 / 自然選択 / 枝分かれ進化 / 大腸腺腫 / 大腸がん / がんゲノム / 次世代シーケンサー

Outline of Final Research Achievements

Intratumor heterogeneity causes therapy resistance of cancer. Advanced colorectal cancer harbors extensive intratumor heterogeneity shaped by neutral evolution. We performed multiregion whole-exome sequencing on 10 early colorectal tumors, which contained adenoma and carcinoma in situ. By comparing with sequencing data from advanced colorectal tumors, we found that the early tumors accumulated a higher proportion of subclonal driver mutations than the advanced tumors. We also observed that variant allele frequencies of subclonal mutations tended to be higher in early tumors, suggesting that the subclonal mutations were subject to selective sweep in early tumorigenesis while neutral evolution is dominant in advanced ones. This study establishes that the evolutionary principle underlying intratumor heterogeneity shifts from Darwinian to neutral evolution during colorectal tumor progression.

Research Products

• [Journal Article] Phosphoserine Phosphatase Is a Novel Prognostic Biomarker on Chromosome 7 in Colorectal Cancer. (2017)
  • Author(s): Sato K, Masuda T, Hu Q, Tobo T, Kidogami S, Ogawa Y, Saito T, Nambara S, Komatsu H, Hirata H, Sakimura S, Uchi R, Hayashi N, Iguchi T, Eguchi H, Ito S, Nakagawa T, Mimori K.
  • Journal Title: Anticancer Res. Volume: 37(5) Pages: 2365-2371
  • Peer Reviewed
• [Journal Article] Attenuated RND1 Expression Confers Malignant Phenotype and Predicts Poor Prognosis in Hepatocellular Carcinoma (2016)
  • Author(s): Komatsu H, Iguchi T, Masuda T, Hirata H, Ueda M, Kidogami S, Ogawa Y, Sato K, Hu Q, Nambara S, Saito T, Sakimura S, Uchi R, Ito S, Eguchi H, Sugimachi K, Eguchi H, Doki Y, Mori M, Mimori K.
  • Journal Title: Ann Surg Oncol. Volume: 24(3) Issue: 3 Pages: 850-859
  • DOI: 10.1245/s10434-016-5573-9
  • Peer Reviewed / Open Access
• [Journal Article] miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients' Susceptibility to Liver Metastasis. (2016)
  • Author(s): Iguchi T, Nambara S, Masuda T, Komatsu H, Ueda M, Kidogami S, Ogawa Y, Hu Q, Sato K, Saito T, Hirata H, Sakimura S, Uchi R, Hayashi N, Ito S, Eguchi H, Sugimachi K, Maehara Y, Mimori K.
  • Journal Title: PLoS One. Volume: 11(11) Issue: 11 Pages: e0165912-e0165912
  • DOI: 10.1371/journal.pone.0165912
  • Peer Reviewed / Open Access
• [Presentation] 腫瘍免疫反応因子と大腸がん再発との関連 (2017)
  • Author(s): 齋藤衆子、﨑村正太郎、長山聡、胡慶江、新井田厚司、増田隆明、鈴木穣、柴田龍弘、宮野悟、三森功士
  • Organizer: 第75回日本癌学会学術集会
• [Presentation] PSPHは7番染色体上に存在する大腸癌の新規ドライバー候補遺伝子である (2016)
  • Author(s): 齋藤衆子、新井田厚司、内龍太郎、平田秀成、江口英利、増田隆明、伊藤修平、林直樹、小松久晃、﨑村正太郎、村上和成、三森功士
  • Organizer: 第75回日本癌学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06