TY - JOUR
T1 - Primordial germ cells as a potential shared cell of origin for mucinous cystic neoplasms of the pancreas and mucinous ovarian tumors
AU - Elias, Kevin M.
AU - Tsantoulis, Petros
AU - Tille, Jean Christophe
AU - Vitonis, Allison
AU - Doyle, Leona A.
AU - Hornick, Jason L.
AU - Kaya, Gurkan
AU - Barnes, Laurent
AU - Cramer, Daniel W.
AU - Puppa, Giacomo
AU - Stuckelberger, Sarah
AU - Hooda, Jagmohan
AU - Dietrich, Pierre Yves
AU - Goggins, Michael
AU - Kerr, Candace L.
AU - Birrer, Michael
AU - Hirsch, Michelle S.
AU - Drapkin, Ronny
AU - Labidi-Galy, Sana Intidhar
N1 - Funding Information:
We thank Mrs Laurence Zulianello for iconographic support. We thank the Genomic platform at the Faculty of Medicine of Geneva for technical support. KME and RD are supported by the Honorable Tina Brozman Foundation. KME is supported by the Robert and Deborah First Family Fund, Saltonstall Research Fund, the Minnesota Ovarian Cancer Alliance, and the Reproductive Scientist Development Program from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) award K12-HD000849. RD is supported by the Dr Miriam and Sheldon G Adelson Medical Research Foundation, the Department of Defense, the Claneil Foundation, and the Run & Walk 4 Family & Friends with Cancer Foundation. JH is supported by the Ann and Sol Schreiber Mentored Investigator Award from the Ovarian Cancer Research Fund Alliance (OCRFA) and the Foundation for Women's Wellness. SS is supported by the Ann and Sol Schreiber Mentored Investigator Award from the OCRFA. SILG is supported by the Research Fund of the Department of Internal Medicine of the Hôpitaux Universitaires de Genève and the Faculty of Medicine of Geneva; this fund receives an unrestricted grant from AstraZeneca Switzerland.
Funding Information:
We thank Mrs Laurence Zulianello for iconographic support. We thank the Genomic platform at the Faculty of Medicine of Geneva for technical support. KME and RD are supported by the Honorable Tina Brozman Foundation. KME is supported by the Robert and Deborah First Family Fund, Saltonstall Research Fund, the Minnesota Ovarian Cancer Alliance, and the Reproductive Scientist Development Program from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) award K12-HD000849. RD is supported by the Dr Miriam and Sheldon G Adelson Medical Research Foundation, the Department of Defense, the Claneil Foundation, and the Run & Walk 4 Family & Friends with Cancer Foundation. JH is supported by the Ann and Sol Schreiber Mentored Investigator Award from the Ovarian Cancer Research Fund Alliance (OCRFA) and the Foundation for Women’s Wellness. SS is supported by the Ann and Sol Schreiber Mentored Investigator Award from the OCRFA. SILG is supported by the Research Fund of the Department of Internal Medicine of the Hôpitaux Universitaires de Genève and the Faculty of Medicine of Geneva; this fund receives an unrestricted grant from AstraZeneca Switzerland.
Publisher Copyright:
Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
PY - 2018/12
Y1 - 2018/12
N2 - Mucinous ovarian tumors (MOTs) morphologically and epidemiologically resemble mucinous cystic neoplasms (MCNs) of the pancreas, sharing a similar stroma and both occurring disproportionately among young females. Additionally, MOTs and MCNs share similar clinical characteristics and immunohistochemical phenotypes. Exome sequencing has revealed frequent recurrent mutations in KRAS and RNF43 in both MOTs and MCNs. The cell of origin for these tumors remains unclear, but MOTs sometimes arise in the context of mature cystic teratomas and other primordial germ cell (PGC) tumors. We undertook the present study to investigate whether non-teratoma-associated MOTs and MCNs share a common cell of origin. Comparisons of the gene expression profiles of MOTs [including both the mucinous borderline ovarian tumors (MBOTs) and invasive mucinous ovarian carcinomas (MOCs)], high-grade serous ovarian carcinomas, ovarian surface epithelium, Fallopian tube epithelium, normal pancreatic tissue, pancreatic duct adenocarcinomas, MCNs, and single-cell RNA-sequencing of PGCs revealed that both MOTs and MCNs are more closely related to PGCs than to either eutopic epithelial tumors or normal epithelia. We hypothesize that MCNs may arise from PGCs that stopped in the dorsal pancreas during their descent to the gonads during early human embryogenesis, while MOTs arise from PGCs in the ovary. Together, these data suggest a common pathway for the development of MCNs and MOTs, and suggest that these tumors may be more properly classified as germ cell tumor variants.
AB - Mucinous ovarian tumors (MOTs) morphologically and epidemiologically resemble mucinous cystic neoplasms (MCNs) of the pancreas, sharing a similar stroma and both occurring disproportionately among young females. Additionally, MOTs and MCNs share similar clinical characteristics and immunohistochemical phenotypes. Exome sequencing has revealed frequent recurrent mutations in KRAS and RNF43 in both MOTs and MCNs. The cell of origin for these tumors remains unclear, but MOTs sometimes arise in the context of mature cystic teratomas and other primordial germ cell (PGC) tumors. We undertook the present study to investigate whether non-teratoma-associated MOTs and MCNs share a common cell of origin. Comparisons of the gene expression profiles of MOTs [including both the mucinous borderline ovarian tumors (MBOTs) and invasive mucinous ovarian carcinomas (MOCs)], high-grade serous ovarian carcinomas, ovarian surface epithelium, Fallopian tube epithelium, normal pancreatic tissue, pancreatic duct adenocarcinomas, MCNs, and single-cell RNA-sequencing of PGCs revealed that both MOTs and MCNs are more closely related to PGCs than to either eutopic epithelial tumors or normal epithelia. We hypothesize that MCNs may arise from PGCs that stopped in the dorsal pancreas during their descent to the gonads during early human embryogenesis, while MOTs arise from PGCs in the ovary. Together, these data suggest a common pathway for the development of MCNs and MOTs, and suggest that these tumors may be more properly classified as germ cell tumor variants.
KW - RHOB
KW - mucinous cystic neoplasm
KW - mucinous ovarian tumor
KW - pathogenesis
KW - primordial germ cells
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U2 - 10.1002/path.5161
DO - 10.1002/path.5161
M3 - Article
C2 - 30229909
AN - SCOPUS:85055278066
SN - 0022-3417
VL - 246
SP - 459
EP - 469
JO - Journal of Pathology
JF - Journal of Pathology
IS - 4
ER -