Distribution of genetic alterations in high-risk early-stage cervical cancer patients treated with postoperative radiation therapy

• Project/Area Number: 18K15654
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: Murakami Naoya 国立研究開発法人国立がん研究センター, 中央病院, 医長 (00604282)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2019: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 子宮頸癌 / 広汎子宮全摘術 / 術後ハイリスク / 術後放射線治療 / 体細胞由来遺伝子変異 / 高リスク群 / 術後補助放射線治療 / 体細胞変異 / 子宮頸がん / 体細胞遺伝子変異 / 放射線感受性 / ゲノム解析

Outline of Final Research Achievements

Between January 2008 and November 2019, 89 patients who underwent abdominal radical hysterectomy followed by post-operative radiation therapy were identified. The follow-up period for living patients was 82.3 months (range, 9.3-153.9), and the 5-year relapse-free survival and overall survival rates were 72.6% and 85.9%, respectively. The most frequently detected somatic mutation was PIK3CA (26 [29.2%] patients); however, no prognostic somatic genetic alterations were identified. Actionable mutations were detected in 30 (33.7%) patients. Actionable mutations were detected in approximately one-third of patients, suggesting that precision medicine can be offered to patients with post-operative high-risk uterine cervical cancer in the near future.

Academic Significance and Societal Importance of the Research Achievements

術後ハイリスク群に術後放射線治療を行った患者を対象とした今回の研究で、子宮頸癌の予後と相関するような遺伝子異常は見いだせなかったが、現時点でのdruggableなactionable mutationは約3割に確認されたのは大きな発見であると考える。今後、子宮頸癌の薬物療法にも分子標的薬が入ってくると思われるが、その際に基盤となる重要な知見が得られたものと考える。。

Research Products

• [Journal Article] Genomic alterations in STK11 can predict clinical outcomes in cervical cancer patients (2020)
  • Author(s): Hirose S, Murakami N, Takahashi K, Kuno I, Takayanagi D, Asami Y, Matsuda M, Shimada Y, Yamano S, Sunami K, Yoshida K, Honda T, Nakahara T, Watanabe T, Komatsu M, Hamamoto R, Kato MK, Matsumoto K, Okuma K, Kuroda T, Okamoto A, Itami J, Kohno T, Kato T, Shiraishi K, Yoshida H
  • Journal Title: Gynecologic Oncology Volume: 156 Issue: 1 Pages: 203-210
  • DOI: 10.1016/j.ygyno.2019.10.022
  • Peer Reviewed