title: Somatic mutation profiling of hobnail variant of papillary thyroid carcinoma.
abstract: Hobnail variant of papillary thyroid carcinoma (HPTC) represents a recently described, aggressive and rare group of thyroid tumors with poorly understood pathogenesis. Molecular data about this group of cancers are few, and a more detailed molecular characterization of these tumors is needed. The main objective of the study is to define a comprehensive molecular typing of HPTC. Eighteen patients affected by HPTC, including eighteen primary tumors and four lymph node metastases, were screened for NRAS, KRAS, HRAS, BRAF, TP53, PIK3CA, hTERT, PTEN, CDKN2A, EGFR, AKT1, CTNNB1 and NOTCH1 gene mutations. Sequencing is conducted on the MiSEQ system, and molecular data are compared with clinical-pathologic data and follow-up. The patients include 14 women and 4 men. Ages range from 23 to 87 years. All 18 primary tumors of HPTC showed ≥30% hobnail features. BRAF and TP53 mutations are by far the most common genetic alterations in primary HPTC (72.2% and 55.6%, respectively), followed by hTERT (44.4%), PIK3CA (27.8%), CTNNB1 (16.7%), EGFR (11.1%), AKT1 (5.5%) and NOTCH1 (5.5%). The mutational pattern in primary tumors and metastasis was usually maintained. Univariate Cox regression analyses with bootstrap procedure indicated a significantly increased mortality risk in patients harboring BRAF mutation and BRAF mutation associated with TP53 and/or PIK3CA mutations. The detection of these multiple mutations appears to allow the identification of a subset of more aggressive tumors within the group and to bear information that should be useful for prognostic stratification of these patients including the planning of adjuvant therapy.
authors.affiliation: Department of Biomedical and Neuromotor SciencesSection of Anatomic Pathology 'M. Malpighi' at Bellaria Hospital, University of Bologna, Bologna, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Morandi
authors.affiliation: Department of PathologyRizzoli Institute, (IRCCS), Bologna, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Righi
authors.affiliation: Department of Medical SciencesUniversity of Turin, Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Maletta
authors.affiliation: Section of Hygiene and BiostatisticsUniversity of Bologna, Bologna, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Rucci
authors.affiliation: Department of PathologyUniversity of Milano Bicocca, Monza, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pagni
authors.affiliation: Oncological Endocrinology UnitDepartment of Medical Sciences, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Gallo
authors.affiliation: Department of PathologyRegional Hospital, Treviso, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Istituto delle Scienze Neurologiche di Bologna (IRCCS)Bellaria Hospital, Bologna, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Caporali
authors.affiliation: Institute for Cancer Research and Treatment (IRCCS)Candiolo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sapino
authors.affiliation: University of Wisconsin School of Medicine and Public HealthMadison, Wisconsin, USA.
authors.forename: Ricardo V
authors.initials: RV
authors.lastname: Lloyd
authors.affiliation: Department of Biomedical and Neuromotor SciencesSection of Anatomic Pathology 'M. Malpighi' at Bellaria Hospital, University of Bologna, Bologna, Italy sofia.asioli3@unibo.it.
authors.forename: Sofia
authors.initials: S
authors.lastname: Asioli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019098:Telomerase / Q000235:genetics; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics
chemical_list: C495270:CTNNB1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C509186:TERT protein, human; D019098:Telomerase
keywords: BRAF; hobnail; next-generation sequencing; papillary thyroid carcinoma