Aneuploidy and RAS mutations are mutually exclusive events in the development of well-differentiated thyroid follicular tumours.
OBJECTIVE
Follicular thyroid tumours present several genetic alterations such as aneuploidy, RAS mutations and PAX8/PPARgammarearrangements. The molecular basis of aneuploidy remains undefined in the majority of human cancers. It has been proposed that mutations in RAS oncogenes could be related to chromosomal instability, although this issue remains controversial. The aim of our study was to investigate the correlation between aneuploidy, RAS mutations and PAX8/PPARgamma gene rearrangement in thyroid follicular tumours.


METHODS
Ploidy status was determined by flow cytometry in 111 thyroid lesions (42 follicular thyroid adenomas, 27 follicular thyroid carcinomas, 19 follicular variants of papillary thyroid carcinoma, 20 poorly differentiated thyroid carcinomas and 3 anaplastic thyroid carcinomas). RAS mutations and PAX8/PPARgamma fusion gene were investigated in 101 and 87 of these samples, respectively.


RESULTS
Altogether, 12 of 50 (24%) diploid tumours presented RAS mutation which contrasts with 3 of 51 (5.9%; P = 0.0124) RAS mutations in the group of aneuploid tumours. The aneuploid tumours harbouring RAS mutations were two poorly differentiated carcinomas and one follicular variant of papillary thyroid carcinoma with poorly differentiated areas. None of the tumours with RAS mutations expressed the PAX8/PPARgamma fusion gene. Three of five (60%) follicular thyroid adenomas and 1 of 7 (14%) follicular thyroid carcinomas, with the PAX8/PPARgamma fusion gene, were aneuploid.


CONCLUSIONS
Our data suggest that aneuploidy and RAS mutations are mutually exclusive events in the development of well-differentiated thyroid follicular tumours.
Banito
Ana
A
Centro de Investigação de Patobiologia Molecular (CIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Lisboa, Portugal.
Pinto
António E
AE
Espadinha
Carla
C
Marques
Ana Rita
AR
Leite
Valeriano
V
D018263:Adenocarcinoma, Follicular / Q000235:genetics*; D000236:Adenoma / Q000235:genetics*; D000782:Aneuploidy; D002277:Carcinoma / Q000235:genetics; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics; D004252:DNA Mutational Analysis; D005434:Flow Cytometry; D015321:Gene Rearrangement; D011905:Genes, ras; D006801:Humans; D015514:Oncogene Proteins, Fusion; D000072636:PAX8 Transcription Factor; D047495:PPAR gamma / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000235:genetics; D017354:Point Mutation; D013223:Statistics as Topic; D013964:Thyroid Neoplasms / Q000235:genetics*
D015514:Oncogene Proteins, Fusion; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D047495:PPAR gamma; D051761:Paired Box Transcription Factors