Circulating tumor DNA functions as an alternative for tissue to overcome tumor heterogeneity in advanced gastric cancer

Abstract

Overcoming tumor heterogeneity is a major challenge for personalized treatment of gastric cancer, especially for human epidermal growth factor receptor‐2 targeted therapy. Analysis of circulating tumor DNA allows a more comprehensive analysis of tumor heterogeneity than traditional biopsies in lung cancer and breast cancer, but little is known in gastric cancer. We assessed mutation profiles of ctDNA and primary tumors from 30 patients with advanced gastric cancer, then performed a comprehensive analysis of tumor mutations by multiple biopsies from five patients, and finally analyzed the concordance of HER2 amplification in ctDNA and paired tumor tissues in 70 patients. By comparing with a single tumor sample, ctDNA displayed a low concordance of mutation profile, only approximately 50% (138/275) somatic mutations were found in paired tissue samples, however, when compared with multiple biopsies, most DNA mutations in ctDNA were also shown in paired tumor tissues. ctDNA had a high concordance (91.4%, Kappa index = 0.784, P < 0.001) of HER2 amplification with tumor tissues, suggesting it might be an alternative for tissue. It implied that ctDNA‐based assessment could partially overcome the tumor heterogeneity, and might serve as a potential surrogate for HER2 analysis in gastric cancer.

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

“…Their work shows the potential of this approach for a broad monitoring of patient treatment as a complementary biopsy tool and for studying tumor clonality. 53 After sequencing the GW-and PL-derived DNA of 6 patients positive for TP53 mutations in their tissue biopsies, we could not observe mutations in 4/6 patients. Due to the high vertical coverage achieved in our study, we can speculate that neoadjuvant chemotherapy was able to diminish and/or eliminate the tumoral clones carrying TP53 mutations in patients where we could not detect them, and in the case of disease progression, mutated tumor clones may have proliferated.…”

“…recently showed in a small cohort of multiple biopsies matched with one plasma sample, that ctDNA might partially mimic tumor heterogeneity. Their work shows the potential of this approach for a broad monitoring of patient treatment as a complementary biopsy tool and for studying tumor clonality …”

PIK3CA mutation profiling in patients with breast cancer, using a highly sensitive detection system

“…Subsequently, we blinded the mutational information of 15 mutant and WT samples, which were tested by an independent researcher using DS and ddPCR. Finally, the concordance among the results of the three methodologies was ascertained, according to a previous report …”

“…Finally, the concordance among the results of the three methodologies was ascertained, according to a previous report. 24 2.7 | Clinical outcome analysis based on PIK3CA mutation information…”

Tumor-specific genetic aberrations in cell-free DNA of gastroesophageal cancer patients

“…The ability of ctDNA analysis to overcome the challenge of intratumor heterogeneity was further investigated in a recent study by Gao and colleges [61].…”