title: Aggressive inherited and sporadic medullary thyroid carcinomas display similar oncogenic pathways.
abstract: RET oncogene mutations are found in familial medullary thyroid carcinomas (MTC) and in one-third of sporadic cases. Oncogenic mechanisms involved in non-RET mutated sporadic MTC remain unclear. To study alterations associated with the development of both inherited and sporadic MTC, pangenomic DNA microarrays were used to analyze the transcriptome of 13 MTCs (four familial and nine sporadic). By using an ANOVA test, a list of 173 gene sequences with at least a twofold change expression was obtained. A subset of differentially expressed genes was controlled by real-time quantitative PCR and immunohistochemistry on a larger collection of MTCs. The expression pattern of those genes allowed us to distinguish two groups of sporadic tumors. The first group displays an expression profile similar to that expressed by inherited RET634 tumors. The second presents an expression profile close to that displayed by inherited RET918 tumors and includes tumors from patients with distant metastases. It is characterized by the overexpression of genes involved in proliferation and invasion (PTN, ESM1, and CEACAM6) or matrix remodeling (COL1A1, COL1A2, and FAP). Interestingly, RET918 tumors showed overexpression of the PTN gene, encoding pleiotrophin, a protein associated with metastasis. Using a MTC cell line, silencing of RET induced the inhibition of PTN gene expression. Overall, our results suggest that familial MTC and sporadic MTC could activate similar oncogenic pathways.
authors.affiliation: CNRS FRE 2939, Institut de Cancérologie Gustave-Roussy, Villejuif, France.
authors.forename: Nabahet
authors.initials: N
authors.lastname: Ameur
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lacroix
authors.forename: Sophie
authors.initials: S
authors.lastname: Roucan
authors.forename: Véronique
authors.initials: V
authors.lastname: Roux
authors.forename: Sophie
authors.initials: S
authors.lastname: Broutin
authors.forename: Monique
authors.initials: M
authors.lastname: Talbot
authors.forename: Corinne
authors.initials: C
authors.lastname: Dupuy
authors.forename: Bernard
authors.initials: B
authors.lastname: Caillou
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Bidart
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes / Q000235:genetics*; D011379:Prognosis; D051096:Proto-Oncogene Proteins c-ret / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D051096:Proto-Oncogene Proteins c-ret