Identification of molecular pathway aberrations in uterine serous carcinoma by genome-wide analyses.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592450
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Shimane University
• Principal Investigator: MIYAZAKI Kohji 島根大学, 医学部, 教授 (50145322)
• Co-Investigator(Kenkyū-buntansha): NAKAYAMA Kentaro 島根大学, 医学部, 講師 (70346401)
• Project Period (FY): 2011 – 2013
• Keywords: 子宮体癌 / ゲノムワイド / がん遺伝子 / がん抑制遺伝子

Research Abstract

We analyzed the genomes of uterine serous carcinoma samples to better understand the molecular genetic characteristics of this cancer. Whole-exome sequencing was performed on 10 uterine serous carcinomas and the matched normal blood or tissue samples. We found frequent somatic mutations in TP53 (81.6%), PIK3CA (23.7%), FBXW7 (19.7%), and PPP2R1A (18.4%) among the 76 uterine serous carcinomas examined. All nine serous carcinomas that had an associated serous endometrial intraepithelial carcinoma had concordant PIK3CA, PPP2R1A, and TP53 mutation status between uterine serous carcinoma and the concurrent serous endometrial intraepithelial carcinoma component. DNA copy number analysis revealed frequent genomic amplification of the CCNE1 locus and deletion of the FBXW7 locus. Nearly half of these uterine serous carcinomas (48%) harbored PIK3CA mutation and/or PIK3CA amplification.

Research Products

• [Journal Article] ESR1 gene amplification in endometrial carcinomas : A clinicopathological analysis (2013)
  • Author(s): Rahman MT, Nakayama K, Rahman M, Ishikawa M, Katagiri H, Katagiri A, Ishibashi T, Sato E, Iida K, Nakayama N, Ishikawa N, Miyazaki K
  • Journal Title: Anticancer Res Volume: 33 Pages: 3775-3781
• [Journal Article] KRAS and MAPK1 gene amplification in type II ovarian carcinomas (2013)
  • Author(s): Rahman MT, Nakayama K, Rahman M, Katagiri H, Katagiri A, Ishibashi T, Ishikawa M, Sato E, Iida K, Nakayama N, Ishikawa N, Miyazaki K
  • Journal Title: Int J Mol Sci Volume: 14 Pages: 13748-13762
• [Journal Article] Fatty acid synthase is a potential therapeutic target in estrogen receptor-/progesterone receptor-positive endometrioid endometrial cancer (2013)
  • Author(s): Rahman MT, Nakayama K, Ishikawa M, Rahman M, Katagiri H, Katagiri A, Ishibashi T, Iida K, Miyazaki K
  • Journal Title: Oncology Volume: 84 Pages: 166-173
• [Journal Article] PPP2R1A mutation is a rare event in ovarian carcinoma across histological subtypes (2013)
  • Author(s): Rahman M, Nakayama K, Rahman MT, Nakayama N, Katagiri H, Katagiri A, Ishibashi T, Ishikawa M, Iida K, Otsuki Y, Nakayama S, Miyazaki K
  • Journal Title: Anticancer Res Volume: 33 Pages: 113-118
• [Journal Article] Is ATP7B a predictive marker in patients with ovarian carcinoma treated with platinum-taxane combination chemotherapy? (2013)
  • Author(s): Katagiri H, Nakayama K, Rahman MT, Rahman M, Katagiri A, Ishibashi T, Ishikawa M, Iida K, Nakayama S, Otsuki Y, Miyazaki K
  • Journal Title: Int J Gynecol Cancer Volume: 23 Pages: 60-64
• [Journal Article] Clinicopathological analysis of loss of AT-rich interactive domain 1A expression in endometrial cancer (2013)
  • Author(s): Rahman M, Nakayama K, Rahman MT, Katagiri H, Katagiri A, Ishibashi T, Ishikawa M, Iida K, Miyazaki K
  • Journal Title: Hum Pathol Volume: 44 Pages: 103-109
• [Journal Article] Low expression of nucleus accumbens-associated protein 1 predicts poor prognosis for patients with pancreatic ductal adenocarcinoma (2012)
  • Author(s): Nishi T, Maruyama R, Urano T, Nakayama N, Kawabata Y, Yano S, Yoshida M, Nakayama K, Miyazaki K, Takenaga K, Tanaka T, Tajima Y
  • Journal Title: Pathol Int Volume: 62 Pages: 802-810
• [Journal Article] eM.: Identification of molecular pathway aberrations in uterine serous carcinoma by genome-wide analyses (2012)
  • Author(s): Kuhn E, Wu RC, Guan B, Wu G, Zhang J, Wang Y, Song L, Yuan X, Wei L, Roden RB, Kuo KT, Nakayama K, Clarke B, Shaw P, Olvera N, Kurman RJ, Levine DA, Wang TL, Shih I
  • Journal Title: J Natl Cancer Inst Volume: 104 Pages: 1503-1513
• [Journal Article] NAC1 is an actin-binding protein that is essential for effective cytokinesis in cancer cells (2012)
  • Author(s): Yap KL, Fraley SI, Thiaville MM, Jinawath N, Nakayama K, Wang J, Wang TL, Wirtz D, Shih IeM
  • Journal Title: Cancer Res Volume: 72 Pages: 4085-4096
• [Journal Article] Notch3 overexpression as potential therapeutic target in advanced stage chemoresistant ovarian cancer (2012)
  • Author(s): Rahman MT, Nakayama K, Rahman M, Katagiri H, Katagiri A, Ishibashi T, Ishikawa M, Iida K, Nakayama S, Otsuki S, Miyazaki K
  • Journal Title: Am J Clin Pathol Volume: 138 Pages: 535-544
• [Journal Article] NAC1, a BTB/POZ protein overexpressed in uterine sarcomas (2012)
  • Author(s): Rahman MT, Nakayama K, Ishikawa M, Rahman M, Katagiri H, Katagiri A, Ishibashi T, Iida K, Yamada T, Miyazaki K
  • Journal Title: Anticancer Res Volume: 32 Pages: 3841-3845
• [Journal Article] Gene amplification of ZNF217 located at chr20q13.2 is associated with lymph node metastasis in ovarian clear cell carcinoma (2012)
  • Author(s): Rahman MT, Nakayama K, Rahman M, Katagiri H, Katagiri A, Ishibashi T, Ishikawa M, Iida K, Nakayama N, Otsuki Y, Nakayama S, Miyazaki K
  • Journal Title: Anticancer Res Volume: 32 Pages: 3091-3095
• [Journal Article] Clinicopathologic and biological analysis of PIK3CA mutation in ovarian clear cell carcinoma (2012)
  • Author(s): Rahman M, Nakayama K, Rahman MT, Nakayama N, Ishikawa M, Katagiri A, Iida K, Nakayama S, Otsuki Y, Shih IeM, Miyazaki K
  • Journal Title: Hum Pathol Volume: 43 Pages: 2197-2206
• [Journal Article] Nuclear localization signal in a cancer-related transcriptional regulator protein NAC1 (2012)
  • Author(s): Okazaki K, Nakayama N, Nariai Y, Nakayama K, Miyazaki K, Maruyama R, Kato H, Kosugi S, Urano T, Sakashita G
  • Journal Title: Carcinogenesis Volume: 33 Pages: 1854-1862
• [Journal Article] Fatty acid synthase expression associated with NAC1 is a potential therapeutic target in ovarian clear cell carcinomas (2012)
  • Author(s): Rahman MT, Nakayama K, Rahman M, Katagiri H, Katagiri A, Ishibashi T, Ishikawa M, Iida K, Nakayama N, Otsuki Y, Nakayama S, Miyazaki K.:
  • Journal Title: Br J Cancer Volume: 107 Pages: 300-307
• [Journal Article] Frequent loss of tumor suppressor ARID1A protein expression in adenocarcinomas/adenosquamous carcinomas of the uterine cervix (2012)
  • Author(s): Katagiri A, Nakayama K, Rahman MT, Rahman M, Katagiri H, Ishikawa M, Ishibashi T, Iida K, Otsuki Y, Nakayama S, Miyazaki K
  • Journal Title: Int J Gynecol Cancer Volume: 22 Pages: 208-212
• [Journal Article] Prognostic and therapeutic impact of the chromosome 20q13.2 ZNF217 locus amplification in ovarian clear cell carcinoma (2012)
  • Author(s): Rahman MT, Nakayama K, Rahman M, Nakayama N, Ishikawa M, Katagiri A, Iida K, Nakayama S, Otsuki Y, Shih IeM, Miyazaki K
  • Journal Title: Cancer Volume: 118 Pages: 2846-2857
  • Peer Reviewed
• [Journal Article] Papadopoulos N, Shih IeM.: Low-grade serous carcinomas of the ovary contain very few point mutations (2012)
  • Author(s): Jones S, Wang TL, Kurman RJ, Nakayama K, Velculescu VE, Vogelstein B, Kinzler KW
  • Journal Title: J Pathol Volume: 226 Pages: 413-420
• [Journal Article] Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma (2012)
  • Author(s): Katagiri A, Nakayama K, Rahman MT, Rahman M, Katagiri H, Nakayama N Ishikawa M, Ishibashi T, Iida K, Otsuki Y, Nakayama S, Miyazaki K
  • Journal Title: Mod Pathol Volume: 25 Pages: 282-288
• [Journal Article] Biological and clinical significance of NAC1 expression in cervical carcinomas : a comparative study between squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas (2012)
  • Author(s): Yeasmin S, Nakayama K, Rahman MT, Rahman M, Ishikawa M, Katagiri A, Iida K, Nakayama N, Otsuki Y, Kobayashi H, Nakayama S, Miyazaki K
  • Journal Title: Hum Pathol Volume: 43 Pages: 506-519
• [Journal Article] EGFR gene amplification is related to adverse clinical outcomes in cervical squamous cell carcinoma, making the EGFR pathway a novel therapeutic target (2011)
  • Author(s): Iida K, Nakayama K, Rahman MT, Rahman M, Ishikawa M, Katagiri A, Yeasmin S, Otsuki Y, Kobayashi H, Nakayama S, Miyazaki K
  • Journal Title: Br J Cancer Volume: 105 Pages: 420-427
• [Journal Article] MKK4 acts as a potential tumor suppressor in ovarian cancer (2011)
  • Author(s): Yeasmin S, Nakayama K, Rahman MT, Rahman M, Ishikawa M, Katagiri A, Iida K, Nakayama N, Miyazaki K
  • Journal Title: Tumour Biol Volume: 32 Pages: 661-670
• [Journal Article] Amplification of the ch19p13.2 NACC1 locus in ovarian high-grade serous carcinoma (2011)
  • Author(s): Shih IeM, Nakayama K, Wu G, Nakayama N, Zhang J, Wang TL
  • Journal Title: Mod Pathol Volume: 24 Pages: 638-645
• [Journal Article] Loss of MKK4 expression in ovarian cancer : a potential role for the epithelial to mesenchymal transition (2011)
  • Author(s): Yeasmin S, Nakayama K, Rahman MT, Rahman M, Ishikawa M, Katagiri A, Iida K, Nakayama N, Miyazaki K
  • Journal Title: Int J Cancer Volume: 128 Pages: 94-104
• [Presentation] 卵巣癌におけるNAC1 pathwayに基づいた創薬への展開、(婦人科がんにおけるトランスレーショナルリサーチ、シーズの探索から臨床応用まで) (2013)
  • Author(s): 中山健太郎、中山真美、石川雅子、片桐浩、片桐敦子、佐藤絵美、飯田幸司、Mohammed Tanjimur Rahman、Munmun Rahman、宮崎康二
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜、横浜市
  • Year and Date: 2013-10-03
• [Presentation] 新規癌関連転写因子NAC1を標的とした卵巣癌治療法の開発、(卵巣癌のMolecular Medicine) (2013)
  • Author(s): 中山健太郎、石川雅子、片桐浩、片桐敦子、石橋朋佳、佐藤絵美、Mohammed Tanjimur Rahman、Munmun Rahman、飯田幸司、中山真美、宮崎康二
  • Organizer: 第54回日本婦人科腫瘍学会
  • Place of Presentation: ホテルグランパシフィックLE DAIBA、東京
  • Year and Date: 2013-07-20
• [Presentation] 卵巣癌におけるNAC1/Gadd45/MKK4経路を介した腹膜播種機構の解明と阻害剤開発による臨床応用、(婦人科癌の浸潤・転移機構の解明と臨床応用) (2013)
  • Author(s): 中山健太郎
  • Organizer: 第65回日本産科婦人科学会学術講演会
  • Place of Presentation: ロイトン札幌(札幌市)
  • Year and Date: 2013-05-10