Histological and mutational profile of diffuse gastric cancer: current knowledge and future challenges

• Tipo: Artigo em Revista Científica Internacional
• Data: 2021

Autores

Garcia Pelaez, J (Autor) Outra; Barbosa Matos, R (Autor) Outra; Gullo, I (Autor) FMUP; Carneiro F (Autor) FMUP; Oliveira, C (Autor) Outra

Revista

Título: Molecular Oncology

ISSN: 1574-7891

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 9 Citações

Scopus - 10 Citações

Outras Informações

ID Authenticus: P-00T-PWF

DOI: 10.1002/1878-0261.12948

Abstract (EN): Gastric cancer (GC) pathogenesis is complex and heterogeneous, reflecting morphological, molecular and genetic diversity. Diffuse gastric cancer (DGC) and intestinal gastric cancer (IGC) are the major histological types. GC may be sporadic or hereditary; sporadic GC is related to environmental and genetic low-risk factors and hereditary GC is caused by inherited high-risk mutations, so far identified only for the diffuse histotype. DGC phenotypic heterogeneity challenges the current understanding of molecular mechanisms underlying carcinogenesis. The definition of a DGC-specific mutational profile remains controversial, possibly reflecting the heterogeneity of DGC-related histological subtypes [signet-ring cell carcinoma (SRCC) and poorly cohesive carcinoma not otherwise specified (PCC-NOS)]. Indeed, DGC and DGC-related subtypes may present specific mutational profiles underlying the particularly aggressive behaviour and dismal prognosis of DGC vs IGC and PCC-NOS vs SRCC. In this systematic review, we revised the histological presentations, molecular classifications and approved therapies for gastric cancer, with a focus on DGC. We then analysed results from the most relevant studies, reporting mutational analysis data specifying mutational frequencies, and their relationship with DGC and IGC histological types, and with specific DGC subtypes (SRCC and PCC-NOS). We aimed at identifying histology-associated mutational profiles with an emphasis in DGC and its subtypes (DGC vs IGC; sporadic vs hereditary DGC; and SRCC vs PCC-NOS). We further used these mutational profiles to identify the most commonly affected molecular pathways and biological functions, and explored the clinical trials directed specifically to patients with DGC. This systematic analysis is expected to expose a DGC-specific molecular profile and shed light into potential targets for therapeutic intervention, which are currently missing.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 27