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
4842 - The analysis of genomic signatures of head and body/tail of pancreatic cancer in Chinese patients
Presenter: Qi Ling
Session: Poster Display session 2
Resources:
Abstract
4988 - MGMT methylation in metastatic pancreatic cancer (mPAC): a single center experience
Presenter: Monica Niger
Session: Poster Display session 2
Resources:
Abstract
5035 - Advantage of three-dimensional image analysis of pancreatic cancer using computed tomography
Presenter: Seung Bae Yoon
Session: Poster Display session 2
Resources:
Abstract
1465 - Phase I study of the oncolytic viral immunotherapy agent Canerpaturev (C-REV) with S-1 in patients with stage IV pancreatic cancer.
Presenter: Susumu Hijioka
Session: Poster Display session 2
Resources:
Abstract
1982 - Impact of anatomic site of biliary tract tumour origin and conditional probability of survival (CS): results from 15 prospective advanced first-line clinical trial
Presenter: Mairead McNamara
Session: Poster Display session 2
Resources:
Abstract
2244 - FOLFOXIRI versus FOLFIRINOX in first-line chemotherapy in patients with advanced pancreatic cancer: a propensity score analysis
Presenter: Angélique Vienot
Session: Poster Display session 2
Resources:
Abstract
4557 - Cellfree tumor-DNA (cfDNA) as a very early predictor of therapeutic outcome in pancreatic ductal adenocarcinoma (PDAC)
Presenter: Sabine Payr
Session: Poster Display session 2
Resources:
Abstract
4406 - Comprehensive genomic profiling (CGP) of gall bladder adenocarcinoma (GBAC) in patients from distinct ancestral populations
Presenter: Milind Javle
Session: Poster Display session 2
Resources:
Abstract
4283 - Phase II Monotherapy Efficacy of Cancer Metabolism Targeting SM-88 in Heavily Pre-Treated PDAC Patients.
Presenter: Allyson Ocean
Session: Poster Display session 2
Resources:
Abstract
2078 - Comprehensive genomic profiling and clinical outcomes in patients (pts) with fibroblast growth factor receptor rearrangement-positive (FGFR2+) cholangiocarcinoma (CCA) treated with pemigatinib in the fight-202 trial
Presenter: Antoine Hollebecque
Session: Poster Display session 2
Resources:
Abstract