Familial small-intestine carcinoids: Chromosomal alterations and germline inositol polyphosphate multikinase sequencing.
BACKGROUND
Familial small-intestine neuroendocrine tumors (SI-NETs) are an exceptional inherited entity. Underlying predisposing mechanisms are unelucidated, but inositol polyphosphate multikinase (IPMK) gene alterations might promote their tumorigenesis.


METHODS
A retrospective-prospective nationwide cohort was constituted, by including patients with proven SI-NETs and at least one relative with the same disease. We performed constitutional and somatic IPMK sequencing, and somatic DNA comparative genomic hybridization (CGH).


RESULTS
We included 17 patients from 8 families, who were characterized by high prevalence (57%) of multiple SI-NETs, and high frequency of distant metastases (82%) and carcinoid syndrome (65%). No IPMK mutation was found in constitutional or tumor DNA. CGH array revealed recurrent chromosome-18 deletions but no alteration in the IPMK region.


CONCLUSIONS
We report here the first European series of patients with familial SI-NETs. Predisposing mechanisms may not involve the IPMK-encoding sequence or chromosomal region and might not differ from those of sporadic SI-NETs.
Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France.
Louis
L
de Mestier
Department of Genetic and Molecular Biology, Cochin University Hospital, APHP, Paris, France; EA7331, Paris Descartes University, Paris, France.
Eric
E
Pasmant
Department of Pathology, Robert-Debré University Hospital, Reims, France.
Clémence
C
Fleury
Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France.
Hedia
H
Brixi
Department of Genetic and Molecular Biology, Cochin University Hospital, APHP, Paris, France; EA7331, Paris Descartes University, Paris, France.
Pierre
P
Sohier
Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France.
Thomas
T
Féron
Department of Pathology, Robert-Debré University Hospital, Reims, France.
Marie-Danièle
MD
Diebold
Department of Genetic and Molecular Biology, Cochin University Hospital, APHP, Paris, France; INSERM U970, Paris Descartes University, Paris, France.
Eric
E
Clauser
Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France. Electronic address: gcadiot@chu-reims.fr.
Guillaume
G
Cadiot
D000328:Adult; D000368:Aged; D002276:Carcinoid Tumor / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D005602:France; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000473:pathology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D011446:Prospective Studies; D012189:Retrospective Studies
D017853:Phosphotransferases (Alcohol Group Acceptor); C434257:inositol polyphosphate multikinase
Carcinoid tumors; Familial; Neuroendocrine tumors; Small intestine