title: Chromosomal aberrations in cell lines derived from thyroid tumors spontaneously developed in TRbetaPV/PV mice.
abstract: The etiology and genetic alterations of follicular thyroid carcinoma are not well understood. By targeting a mutation (PV) into the thyroid hormone receptor beta gene (TRbetaPV mouse), we created a knock-in mutant TRbeta(PV/PV) mouse that spontaneously develop follicular thyroid carcinoma with progression to metastasis similar to human follicular thyroid carcinoma. This mouse model provides a valuable tool to ascertain the nature and the extent of genomic rearrangements that occur during carcinogenesis of the thyroid. Spectral karyotyping analysis (SKY) of seven cell lines derived from thyroid tumors developed in TRbeta(PV/PV) mice showed that all of them had abnormal karyotypes, with chromosome number ranging from near-diploid (39-42 chromosomes) to hypotetraploid (63-79 chromosomes). These seven cell lines also exhibited a variety of structural chromosomal aberrations, including common recurrent translocations and deletions. This SKY analysis shows that the development and progression of follicular thyroid carcinoma in knock-in TRbeta(PV/PV) mutant mice comprise recurrent structural and numerical genomic changes, some of which mimic those described in human thyroid cancer.
authors.affiliation: Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, 37 Convent Drive MSC 4262, Building 37/Room 4128C, Bethesda, MD 20892-4262, USA. drazen_zimonjic@nih.gov
authors.forename: Drazen B
authors.initials: DB
authors.lastname: Zimonjic
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Kato
authors.forename: Hao
authors.initials: H
authors.lastname: Ying
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Popescu
authors.forename: Sheue-Yann
authors.initials: SY
authors.lastname: Cheng
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D032681:Spectral Karyotyping; D013954:Thyroglobulin / Q000032:analysis; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D037042:Thyroid Hormone Receptors beta; D013954:Thyroglobulin