Virchows Archiv

, Volume 475, Issue 5, pp 659–663 | Cite as

Identification of a novel PRR15L-RSPO2 fusion transcript in a sigmoid colon cancer derived from superficially serrated adenoma

  • Yasuhiko Mizuguchi
  • Taku Sakamoto
  • Taiki Hashimoto
  • Shunsuke Tsukamoto
  • Satoru Iwasa
  • Yutaka Saito
  • Shigeki SekineEmail author
Brief Report


Superficially serrated adenoma (SuSA) is a recently proposed subtype of colorectal serrated lesion. We here report a sigmoid colon cancer derived from SuSA, which exhibited aggressive clinical behavior. Endoscopically, the tumor appeared as a superficial elevated lesion with a large nodule. Histological examination of the surgically resected material showed tubular adenocarcinoma associated with SuSA. Although tumor invasion was limited to the submucosal layer, lymph node and extranodal metastases were detected. The patient subsequently developed peritoneal metastases and died 15 months after surgery. Molecular analyses identified a KRAS mutation and a novel PRR15L-RSPO2 fusion, which retains the entire coding region of RSPO2, in both SuSA and adenocarcinoma components. The present study demonstrates the malignant potential of SuSA and expands the spectrum of RSPO fusions in colorectal neoplasms.


Colorectal cancer R-spondin Superficially serrated adenoma KRAS 



We thank Ms. Reiko Ogawa, Ms. Sachiko Miura, and Ms. Toshiko Sakaguchi for their skillful technical assistance.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Bettington M, Walker N, Clouston A, Brown I, Leggett B, Whitehall V (2013) The serrated pathway to colorectal carcinoma: current concepts and challenges. Histopathology 62:367–386. CrossRefPubMedGoogle Scholar
  2. 2.
    Snover DC, Ahnen DJ, Burt RW (2010) Serrated polyps of the colon and rectum and serrated polyposis. In: Bosman FT, Carneiro F, Hruban RH et al (eds) WHO classification of tumours of the digestive system, pp 160–165Google Scholar
  3. 3.
    Rex DK, Ahnen DJ, Baron JA, Batts KP, Burke CA, Burt RW, Goldblum JR, Guillem JG, Kahi CJ, Kalady MF, O′Brien MJ, Odze RD, Ogino S, Parry S, Snover DC, Torlakovic EE, Wise PE, Young J, Church J (2012) Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol 107:1315–1329. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Hashimoto T, Tanaka Y, Ogawa R, Mori T, Yoshida H, Taniguchi H, Hiraoka N, Kojima M, Oono Y, Saito Y, Sekine S (2018) Superficially serrated adenoma: a proposal for a novel subtype of colorectal serrated lesion. Mod Pathol 31:1–11. CrossRefGoogle Scholar
  5. 5.
    Hashimoto T, Yamashita S, Yoshida H, Taniguchi H, Ushijima T, Yamada T, Saito Y, Ochiai A, Sekine S, Hiraoka N (2017) WNT pathway gene mutations are associated with the presence of dysplasia in colorectal sessile serrated adenoma/polyps. Am J Surg Pathol 41:1188–1197. CrossRefPubMedGoogle Scholar
  6. 6.
    Sekine S, Yamashita S, Tanabe T, Hashimoto T, Yoshida H, Taniguchi H, Kojima M, Shinmura K, Saito Y, Hiraoka N, Ushijima T, Ochiai A (2016) Frequent PTPRK-RSPO3 fusions and RNF43 mutations in colorectal traditional serrated adenoma. J Pathol 239:133–138. CrossRefPubMedGoogle Scholar
  7. 7.
    Sekine S, Ogawa R, Hashimoto T, Motohiro K, Yoshida H, Taniguchi H, Saito Y, Yasuhiro O, Ochiai A, Hiraoka N (2017) Comprehensive characterization of RSPO fusions in colorectal traditional serrated adenomas. Histopathology 71:601–609. CrossRefPubMedGoogle Scholar
  8. 8.
    Seshagiri S, Stawiski EW, Durinck S, Modrusan Z, Storm EE, Conboy CB, Chaudhuri S, Guan Y, Janakiraman V, Jaiswal BS, Guillory J, Ha C, Dijkgraaf GJP, Stinson J, Gnad F, Huntley MA, Degenhardt JD, Haverty PM, Bourgon R, Wang W, Koeppen H, Gentleman R, Starr TK, Zhang Z, Largaespada DA, Wu TD, de Sauvage FJ (2012) Recurrent R-spondin fusions in colon cancer. Nature 488:660–664. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Li C, Cao J, Zhang N, Tu M, Xu F, Wei S, Chen X, Xu Y (2018) Identification of RSPO2 fusion mutations and target therapy using a porcupine inhibitor. Sci Rep 8:1–9. CrossRefGoogle Scholar
  10. 10.
    Hashimoto T, Ogawa R, Yoshida H, Taniguchi H, Kojima M, Saito Y, Sekine S (2019) EIF3E- RSPO2and PIEZO1- RSPO2fusions in colorectal traditional serrated adenoma. In: Histopathology his.13867. CrossRefGoogle Scholar
  11. 11.
    Storm EE, Durinck S, de Sousa e Melo F, Tremayne J, Kljavin N, Tan C, Ye X, Chiu C, Pham T, Hongo JA, Bainbridge T, Firestein R, Blackwood E, Metcalfe C, Stawiski EW, Yauch RL, Wu Y, de Sauvage FJ (2016) Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function. Nature 529:97–100. CrossRefPubMedGoogle Scholar
  12. 12.
    Kloosterman WP, Coebergh van den Braak RRJ, Pieterse M et al (2017) A systematic analysis of oncogenic gene fusions in primary colon cancer. Cancer Res 77:3814–3822. CrossRefPubMedGoogle Scholar
  13. 13.
    Shinmura K, Kahyo T, Kato H, Igarashi H, Matsuura S, Nakamura S, Kurachi K, Nakamura T, Ogawa H, Funai K, Tanahashi M, Niwa H, Sugimura H (2014) RSPO fusion transcripts in colorectal cancer in Japanese population. Mol Biol Rep 41:5375–5384. CrossRefPubMedGoogle Scholar
  14. 14.
    Bettington M, Rosty C, Whitehall V, Leggett B, McKeone D, Pearson SA, Walker N (2018) A morphological and molecular study of proposed early forms of traditional serrated adenoma. Histopathology 73:1023–1029. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Endoscopy DivisionNational Cancer Center HospitalTokyoJapan
  2. 2.Division of Pathology and Clinical LaboratoriesNational Cancer Center HospitalTokyoJapan
  3. 3.Division of Colorectal SurgeryNational Cancer Center HospitalTokyoJapan
  4. 4.Division of Gastrointestinal Medical OncologyNational Cancer Center HospitalTokyoJapan
  5. 5.Division of Molecular PathologyNational Cancer Center Research InstituteTokyoJapan

Personalised recommendations