Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 145, Issue 4, Pages 1090-1098Publisher
WILEY
DOI: 10.1002/ijc.32217
Keywords
gastric cancer; liquid biopsy; TP53
Categories
Funding
- Associacao Beneficente Alzira Denise Hertzog Silva (ABADHS)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (Capes)
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [14/26897-0]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [14/26897-0] Funding Source: FAPESP
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Whereas cancer patients have benefited from liquid biopsies, the scenario for gastric adenocarcinoma (GAC) is still dismal. We used next-generation deep sequencing of TP53-a highly mutated and informative gene in GAC-to assess mutations in tumor biopsies, plasma (PL) and stomach fluids (gastric wash-GW). We evaluated their potential to reveal tumor-derived mutations, useful for monitoring mutational dynamics at diagnosis, progression and treatment. Exon-capture libraries were constructed from 46 patients including tumor biopsies, GW and PL pre and post-treatment (196 samples), with high vertical coverage >8,000x. At diagnosis, we detected TP53 mutations in 15/46 biopsies (32.6%), 7/46 GW- (15.2%) and 6/46 PL-samples (13%). Biopsies and GW were concordant in 38/46 cases (82.6%) for the presence/absence of mutations and, furthermore, four GW-exclusive mutations were identified, suggesting tumor heterogeneity. Considering the combined analysis of GW and PL, TP53 mutations found in biopsies were also identified in 9/15 (60%) of cases, the highest detection level reported for GAC. Our study indicates that GW could be useful to track DNA alterations, especially if anchored to a comprehensive gene-panel designed for this malignancy.
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