Aggressive inherited and sporadic medullary thyroid carcinomas display similar oncogenic pathways.
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.
Ameur
Nabahet
N
CNRS FRE 2939, Institut de Cancérologie Gustave-Roussy, Villejuif, France.
Lacroix
Ludovic
L
Roucan
Sophie
S
Roux
Véronique
V
Broutin
Sophie
S
Talbot
Monique
M
Dupuy
Corinne
C
Caillou
Bernard
B
Schlumberger
Martin
M
Bidart
Jean-Michel
JM
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
D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D051096:Proto-Oncogene Proteins c-ret