Abstract 3182
Background
Clonal hematopoiesis (CH) leads to blood-derived somatic mutations in KRAS, NRAS and BRAF. Our aim is to identify the prevalence of CH-derived mutations in these three genes in metastatic colorectal cancer (mCRC) patients and reveal the practical clinical implication of these mutations on plasma cell-free DNA (cfDNA) genotyping.
Methods
We analyzed KRAS, NRAS and BRAF genotypes in plasma and matched tumor tissues of 236 mCRC patients through next-generation sequencing (NGS). Suspected CH mutations were defined as those only present in plasma with variant allelic frequencies (AFs) <5% and were confirmed by paired peripheral blood cells (PBCs) using droplet digital PCR (ddPCR). The hemopoietic lineage harboring a CH-derived mutation was analyzed through flow cytometry.
Results
We identified suspected CH mutations in twenty patients (8.4%, 20/236). Three of these patients (1.27%, 3/236) had a CH-derived KRAS mutation. Two of them had a KRAS G12X and the third had a KRAS Q61H. We did not detect CH-derived NRAS or BRAF mutations. Patients harboring a CH-derived mutation previously received chemotherapy treatment. In one CH-derived KRAS G12X case, the mutation was enriched in lymphocytes and persisted in cfDNA over the course of 4 months of therapy.
Conclusions
We confirmed the existence of CH-derived KRAS mutations in a small proportion of mCRC patients. This should be noted to prevent misclassification as tumor somatic mutations when performing cfDNA sequencing.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The National Natural Science Foundation of China (81572064, 81772263, 81772511, 81602038), the Key Developing Disciplines of Shanghai Municipal Commission of Health and Family Planning (2015ZB0201), the Projects from the Shanghai Science and Technology Commission (16411952100), the Projects from Zhongshan Hospital, Fudan University (2018ZSLC05).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4317 - Prognostic factors analysis of 343 patients with adenocarcinoma of esophagogastric junction
Presenter: Yixun Lu
Session: Poster Display session 2
Resources:
Abstract
4099 - Effects of preoperative preparation time on efficacy of neoadjuvant chemotherapy (SOX) in patients with advanced gastric cancer
Presenter: Xinxin Wang
Session: Poster Display session 2
Resources:
Abstract
3769 - The prognostic value of higher absolute lymphocyte counts for patients with surgically resected non-advanced gastric cancer
Presenter: Se Jun Park
Session: Poster Display session 2
Resources:
Abstract
1718 - Trastuzumab and pertuzumab added to neoadjuvant chemoradiotherapy in resectable HER2+ esophageal adenocarcinoma patients: an update on survival and predictive biomarkers in the TRAP study
Presenter: Charlotte Stroes
Session: Poster Display session 2
Resources:
Abstract
5403 - Interim analysis of a phase II trial of perioperative chemotherapy plus avelumab in esophagogastric and gastric adenocarcinoma
Presenter: Thierry Alcindor
Session: Poster Display session 2
Resources:
Abstract
591 - Evaluation of the introduction of primary G-CSF prophylaxis to the FLOT chemotherapy regimen.
Presenter: Kelly-Marie Crampton
Session: Poster Display session 2
Resources:
Abstract
1402 - Subgroup analyses of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with 2 and 4 courses of cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) as neoadjuvant chemotherapy for locally advanced gastric cancer
Presenter: Tsutomu Hayashi
Session: Poster Display session 2
Resources:
Abstract
3743 - HER2 Copy Number as Predictor of Disease-Free Survival in HER2-Positive Resectable Gastric Cancer
Presenter: Zimin Liu
Session: Poster Display session 2
Resources:
Abstract
2032 - Effect of neoadjuvant chemotherapy on the Programmed Death-1 pathway in esophageal and gastric cancer
Presenter: Maria Svensson
Session: Poster Display session 2
Resources:
Abstract
4304 - A user-friendly nomogram to predict relapse-free survival (RFS) in western patients with resected gastric cancer (GC)
Presenter: Massimiliano Salati
Session: Poster Display session 2
Resources:
Abstract