Publications

Authors:

Fassan, M; Simbolo, Michele; Bria, Emilio; Mafficini, A; Pilotto, Sara; Capelli, Paola; Bencivenga, M; Pecori, Sara; Luchini, Claudio; Neves, D; Turri, G; Vicentini, C; Montagna, Licia; Tomezzoli, Anna; Tortora, Giampaolo; Chilosi, Marco; DE MANZONI, Giovanni; Scarpa, Aldo

Title:

High-throughput mutation profiling identifies novel molecular dysregulation in high-grade intraepithelial neoplasia and early gastric cancers

Year:

2014

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

Sì

Name of journal:

Gastric Cancer

ISSN of journal:

1436-3291

N° Volume:

17

Number or Folder:

3

Page numbers:

442-449

Keyword:

Gastric carcinogenesis; Intraepithelial neoplasia; Early gastric cancer Next-generation sequencing; Biomarkers

Short description of contents:

BACKGROUND: There is still no widely accepted molecular marker available to distinguish between gastric high-grade intraepithelial neoplasia (HG-IEN) and invasive early gastric cancer (EGC). METHODS: HG-IEN and EGC lesions coexisting in the same patient were manually microdissected from a series of 15 gastrectomies for EGC; 40 ng DNA was used for multiplex PCR amplification using the Ion AmpliSeq Cancer Panel, which explores the mutational status of hotspot regions in 50 cancer-associated genes. RESULTS: Of the 15 EGCs, 12 presented at least one somatic mutation among the 50 investigated genes, and 6 of these showed multiple driver gene somatic mutations. TP53 mutations were observed in 9 cases; APC mutations were identified in 3 cases; and ATM and STK11 were mutated in 2 cases. Seven HG-IEN lesions shared an identical mutational profile with the EGC from the same patient; 13 mutations observed in APC, ATM, FGFR3, PIK3CA, RB1, STK11, and TP53 genes were shared by both HG-IEN and ECG lesions. CDKN2A, IDH2, MET, and RET mutations were observed only in EGC. TP53 deregulation was further investigated in an independent series of 75 biopsies corresponding to all the phenotypic lesions occurring in the EGC carcinogenetic cascade. p53 nuclear immunoreaction progressively increased along with the dedifferentiation of the lesions (P < 0.001). Overall, 18 of 20 p53-positive lesions showed a TP53 mutated gene. DISCUSSION: Our results support the molecular similarity between HG-IEN and EGC and suggest a relevant role for TP53 in the progression to the invasive phenotype and the use of immunohistochemistry as a surrogate to detect TP53 gene mutations.

Product ID:

80278

Handle IRIS:

11562/636751

Deposited On:

February 25, 2015

Last Modified:

November 15, 2022

Bibliographic citation:

Fassan, M; Simbolo, Michele; Bria, Emilio; Mafficini, A; Pilotto, Sara; Capelli, Paola; Bencivenga, M; Pecori, Sara; Luchini, Claudio; Neves, D; Turri, G; Vicentini, C; Montagna, Licia; Tomezzoli, Anna; Tortora, Giampaolo; Chilosi, Marco; DE MANZONI, Giovanni; Scarpa, Aldo, High-throughput mutation profiling identifies novel molecular dysregulation in high-grade intraepithelial neoplasia and early gastric cancers «Gastric Cancer» , vol. 17 , n. 3 , 2014 , pp. 442-449

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