Identification of a paired box gene 8-peroxisome proliferator-activated receptor gamma (PAX8-PPAR gamma) rearrangement mosaicism in a patient with an autonomous functioning follicular thyroid carcinoma bearing an activating mutation in the TSH receptor

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Lado Abeal, J (Author) Other; Celestino, R (Author) Other; Bravo, SB (Author) Other; Garcia Rendueles, MER (Author) Other; de la Calzada, J (Author) Other; Castro, I (Author) Other; Castro, P (Author) FMUP; Espadinha, C (Author) Other; Palos, F (Author) Other; Soares, P (Author) FMUP; Alvarez, CV (Author) Other; Sobrinho Simoes, M (Author) FMUP; Cameselle Teijeiro, J (Author) Other

Journal

Title: Endocrine-Related Cancer

Vol. 17

Pages: 599-610

ISSN: 1351-0088

Publisher: BioScientifica Ltd.

Indexing

ISI Web of Knowledge - 13 Citations

Scopus - 15 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-003-380

DOI: 10.1677/erc-09-0069

Abstract (EN): Our main objective was to search for mutations in candidate genes and for paired box gene 8-peroxisome proliferator-activated receptor gamma (PAX8-PPAR gamma) rearrangement in a well-differentiated angioinvasive follicular thyroid carcinoma (FTC) causing hyperthyroidism. DNA and RNA were extracted from the patient's thyroid tumor, as well as 'normal' thyroid tissue, and from peripheral blood lymphocytes (PBLs) of the patient, her daughter, and two siblings. Nuclear isolation was extracted from the patient's tumor, 'normal' thyroid tissue, PBLs, and uterine leiomyoma tissue. TSH receptor (TSHR), RAS, and BRAF genes were sequenced. We searched for PAX8-PPAR gamma in thyroid, PBL, and uterine leiomyoma samples from the patient and family members. Proliferative effects of detected mutants on non-transformed human thyrocytes cultures. An activating TSHR mutation, M453T, was detected in the tumor. PAX8(exons 1-8+10)-PPAR gamma was found in all tested patient's tissues. A second rearrangement, PAX8(exons 1-8)-PPAR gamma, was detected in the patient's normal thyroid tissue. Under deprived medium condition, co-transfection of PAX8-PPAR gamma and TSHR-M453T dramatically increased the number of thyrocytes, an effect that it was not observed with TSHR wild-type (WT); under complete medium conditions, co-transfection of PAX8-PPAR gamma with either TSHR-M453T or TSHR-WT inhibited cell proliferation. We report a patient with hyperthyroidism due to a FTC bearing an activating TSHR mutation and PAX8-PPAR gamma rearrangements. PAX8-PPAR gamma was present as a mosaicism affecting tissues from endodermal and mesodermal origin. PAX8-PPAR gamma and TSHR-M453T inhibited or promoted thyrocyte proliferation depending on medium conditions. The activating TSHR mutation could promote in vivo FTC development in PAX8-PPAR gamma-positive thyrocytes under poor blood supply with deprivation of growth factors but restraint the tumor growth when growth factors are supplied. Endocrine-Related Cancer (2010) 17 599-610

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12