title: Genetic Heterogeneity of HER2 Amplification and Telomere Shortening in Papillary Thyroid Carcinoma.
abstract: Extensive research is dedicated to understanding if sporadic and familial papillary thyroid carcinoma are distinct biological entities. We have previously demonstrated that familial papillary thyroid cancer (fPTC) cells exhibit short relative telomere length (RTL) in both blood and tissues and that these features may be associated with chromosome instability. Here, we investigated the frequency ofHER2(Human Epidermal Growth Factor Receptor 2) amplification, and other recently reported genetic alterations in sporadic PTC (sPTC) and fPTC, and assessed correlations with RTL andBRAFmutational status. We analyzedHER2gene amplification and the integrity ofALK,ETV6,RET, andBRAFgenes by fluorescence in situ hybridization in isolated nuclei and paraffin-embedded formalin-fixed sections of 13 fPTC and 18 sPTC patients. We analyzedBRAFV600Emutation and RTL by qRT-PCR. SignificantHER2amplification (p= 0.0076), which was restricted to scattered groups of cells, was found in fPTC samples.HER2amplification in fPTCs was invariably associated withBRAFV600Emutation. RTL was shorter in fPTCs than sPTCs (p< 0.001). No rearrangements of other tested genes were observed. These findings suggest that the association ofHER2amplification withBRAFV600Emutation and telomere shortening may represent a marker of tumor aggressiveness, and, in refractory thyroid cancer, may warrant exploration as a site for targeted therapy.
authors: Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato 09042, Italy. paola.caria@unica.it.
authors: Paola
authors: P
authors: Caria
authors: Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena 53100, Italy. cantara@unisi.it.
authors: Silvia
authors: S
authors: Cantara
authors: Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato 09042, Italy. dvfrau@unica.it.
authors: Daniela Virginia
authors: DV
authors: Frau
authors: Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena 53100, Italy. pacini8@unisi.it.
authors: Furio
authors: F
authors: Pacini
authors: Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato 09042, Italy. vanni@unica.it.
authors: Roberta
authors: R
authors: Vanni
authors: Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato 09042, Italy. dettorit@unica.it.
authors: Tinuccia
authors: T
authors: Dettori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D015321:Gene Rearrangement; D018740:Genetic Heterogeneity; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D059506:Telomere Shortening / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D000077548:Anaplastic Lymphoma Kinase; D048493:Proto-Oncogene Proteins B-raf; D050783:Proto-Oncogene Proteins c-ets; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C000626173:ALK protein, human; C508053:ERBB2 protein, human; C099282:RET protein, human; C482119:BRAF protein, human
keywords: FISH (fluorescence in situ hybridization); HER2 (Human Epidermal Growth Factor Receptor 2); Telomere; papillary thyroid carcinoma