Integrated genomic characterization of papillary thyroid carcinoma. Academic Article uri icon

Overview

MeSH

  • DNA Copy Number Variations
  • Gene Fusion
  • Humans
  • Thyroid Gland

MeSH Major

  • Carcinoma
  • Mutation
  • Thyroid Neoplasms

abstract

  • Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here, we describe the genomic landscape of 496 PTCs. We observed a low frequency of somatic alterations (relative to other carcinomas) and extended the set of known PTC driver alterations to include EIF1AX, PPM1D, and CHEK2 and diverse gene fusions. These discoveries reduced the fraction of PTC cases with unknown oncogenic driver from 25% to 3.5%. Combined analyses of genomic variants, gene expression, and methylation demonstrated that different driver groups lead to different pathologies with distinct signaling and differentiation characteristics. Similarly, we identified distinct molecular subgroups of┬áBRAF-mutant tumors, and multidimensional analyses highlighted a potential involvement of oncomiRs in less-differentiated subgroups. Our results propose a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties, which has the potential to improve their pathological classification and better inform the management of the disease.

authors

publication date

  • October 23, 2014

has subject area

  • Carcinoma
  • DNA Copy Number Variations
  • Gene Fusion
  • Humans
  • Mutation
  • Thyroid Gland
  • Thyroid Neoplasms

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4243044

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2014.09.050

PubMed ID

  • 25417114

Additional Document Info

start page

  • 676

end page

  • 690

volume

  • 159

number

  • 3