Identification of a novel PRR15L-RSPO2 fusion transcript in a sigmoid colon cancer derived from superficially serrated adenoma
- 215 Downloads
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.
KeywordsColorectal 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.
- 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.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. https://doi.org/10.1038/ajg.2012.161 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1097/PAS.0000000000000877 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1002/path.4709 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1038/nature11282 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1038/nature16466 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1007/s11033-014-3409-x CrossRefPubMedGoogle Scholar