| Autor: |
Pizzi, Melissa Pool, Bartelli, Thais Fernanda, Pelosof, Adriane Graicer, Freitas, Helano Carioca, Begnami, Maria Dirlei, Abrantes, Lais Lie Senda, Sztokfisz, Claudia, Valieris, Renan, Knebel, Franciele Hinterholz, Coelho, Luiz Gonzaga Vaz, Costa, Wilson Luiz, Coimbra, Felipe J.F., Silva, Israel Tojal, Amorim, Maria Galli, Nunes, Diana Noronha, Dias‐Neto, Emmanuel |
| Předmět: |
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| Zdroj: |
International Journal of Cancer; Aug2019, Vol. 145 Issue 4, p1090-1098, 9p |
| Abstrakt: |
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 >8,000×. 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. What's new? The detection of mutations in gastric adenocarcinoma (GAC) potentially can facilitate diagnosis and treatment. A promising means of GAC mutation detection is liquid biopsy from plasma and gastric fluids, though these approaches have yet to be fully explored in GAC. Here, deep sequencing of gastric wash‐derived DNA from GAC patients revealed 11 different TP53 mutations, four of which were absent from original primary tumor biopsies, suggesting possible tumor heterogeneity. Analysis of plasma and gastric washes collected after treatment in these patients revealed increased rates of TP53 mutation, indicating a possible role for liquid biopsy in GAC monitoring during treatment. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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