Whole-exome sequencing identified the genetic origin of a mucinous neoplasm in a mature cystic teratoma.
Mucinous tumour arising from a mature cystic teratoma associated with pseudomyxoma peritonei (PMP) is a rare disease and its tissue origin is not easy to specify by conventional histological and immunohistochemical analyses. To identify the origin of a secondary tumour arising from a mature teratoma, we performed whole-exome sequencing of a PMP secondary to a primary ovarian mucinous tumour. The mucinous tumour was CK20 (+), CK7 (-) and CDX2 (+). Its genome harboured 28 somatic non-silent mutations (27 missense and 1 nonsense) that included eight putative driver gene mutations catalogued in COSMIC database (KRAS, GNAS, ZBTB38, ENAM, HTR5A, BAI1, ADAMTS8 and RASA3). KRAS mutation as well as mutations in genes that antagonise RAS signalling (RASA3 and ADAMTS8) suggest that alterations in RAS signalling may play a role in its development. More importantly, the concurrent KRAS and GNAS hotspot mutations, and CK20 (+), CK7 (-) and CDX2 (+) expression strongly indicated its appendiceal origin. Our results indicate that next-generation sequencing combined with histological and immunohistochemical analyses may be a better strategy than the conventional analyses alone to identify the origin of a secondary tumour arising from a mature teratoma. Also, the data suggest that a PMP secondary to a primary ovarian mucinous tumour genome arising in the teratoma may recapitulate the mutational features of appendiceal mucinous tumours.
Department of Pathology, The Catholic University of Korea, Seoul, Republic of Korea; Department of Cancer Evolution Research Center, The Catholic University of Korea, Seoul, Republic of Korea.
Youn Jin
YJ
Choi
Department of Hospital Pathology, The Catholic University of Korea, Seoul, Republic of Korea.
Sung Hak
SH
Lee
Department of Pathology, The Catholic University of Korea, Seoul, Republic of Korea; Department of Cancer Evolution Research Center, The Catholic University of Korea, Seoul, Republic of Korea.
Min Sung
MS
Kim
Department of Cancer Evolution Research Center, The Catholic University of Korea, Seoul, Republic of Korea; Integrated Research Center for Genome Polymorphism, The Catholic University of Korea, Seoul, Republic of Korea.
Seung-Hyun
SH
Jung
Department of Gynecology/Obstetrics, The Catholic University of Korea, Seoul, Republic of Korea.
Soo Young
SY
Hur
Integrated Research Center for Genome Polymorphism, The Catholic University of Korea, Seoul, Republic of Korea; Department of Microbiology, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: yejun@catholic.ac.kr.
Yeun-Jun
YJ
Chung
Department of Pathology, The Catholic University of Korea, Seoul, Republic of Korea; Department of Cancer Evolution Research Center, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: suhulee@catholic.ac.kr.
Sug Hyung
SH
Lee
D004252:DNA Mutational Analysis / Q000379:methods; D059472:Exome; D005260:Female; D006801:Humans; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000473:pathology; D011553:Pseudomyxoma Peritonei / Q000235:genetics* / Q000473:pathology; D013724:Teratoma / Q000235:genetics* / Q000473:pathology
Ovarian neoplasm; mucinous tumour; mutation; pseudomyxoma peritonei; teratoma