Identification of DNA mutations in gastric washes from gastric adenocarcinoma patients: Possible implications for liquid biopsies and patient follow-up

Author(s):Show less -

Pizzi, Melissa Pool ^[1] ; Bartelli, Thais Fernanda ^[1] ; Pelosof, Adriane Graicer ^[2] ; Freitas, Helano Carioca ^{[3, 1]} ; Begnami, Maria Dirlei ^[4] ; Senda de Abrantes, Lais Lie ^[5] ; Sztokfisz, Claudia ^[2] ; Valieris, Renan ^[6] ; Knebel, Franciele Hinterholz ^[7] ; Vaz Coelho, Luiz Gonzaga ^[8] ; da Costa, Wilson Luiz ^[9] ; Coimbra, Felipe J. F. ^[9] ; da Silva, Israel Tojal ^[6] ; de Amorim, Maria Galli ^[1] ; Nunes, Diana Noronha ^[1] ; Dias-Neto, Emmanuel ^{[1, 10]}

Affiliation

^[1] AC Camargo Canc Ctr, Lab Med Genom, Tagua St, 440 Liberdade, Sao Paulo, SP - Brazil

^[2] AC Camargo Canc Ctr, Endoscopy Sect, Sao Paulo, SP - Brazil

^[3] AC Camargo Canc Ctr, Dept Clin Oncol, Sao Paulo, SP - Brazil

^[4] AC Camargo Canc Ctr, Dept Pathol, Sao Paulo, SP - Brazil

^[5] AC Camargo Canc Ctr, Int Res Ctr, Sao Paulo, SP - Brazil

^[6] AC Camargo Canc Ctr, Lab Computat Biol, Sao Paulo, SP - Brazil

^[7] Hosp Sirio Libanes, Ctr Oncol Mol, Sao Paulo, SP - Brazil

^[8] Univ Fed Minas Gerais, Hosp Clin, Fac Med, Inst Alfa Gastroenterol, Belo Horizonte, MG - Brazil

^[9] AC Camargo Canc Ctr, Dept Abdominal Surg, Sao Paulo, SP - Brazil

^[10] Univ Sao Paulo, Fac Med, Inst Psiquiatria, Lab Neurosci Alzira Denise Hertzog Silva LIM 27, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: International Journal of Cancer; v. 145, n. 4, p. 1090-1098, AUG 15 2019.
• Web of Science Citations: 3

Abstract

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. (AU)

• FAPESP's process: 14/26897-0 - Epidemiology and genomics of gastric adenocarcinomas in Brazil
• Grantee: Emmanuel Dias-Neto
• Support Opportunities: Research Projects - Thematic Grants