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
1988 - Molecular profiling reveals novel targetable biomarkers in neuroendocrine carcinoma of the uterine cervix
Presenter: Semir Vranic
Session: Poster Display session 2
Resources:
Abstract
2672 - Changes in clinico-pathological characteristics of vulvar cancer in Japan: increasing oldest-old, stage-shifting, and decreasing cohort-level survival
Presenter: Shin Nishio
Session: Poster Display session 2
Resources:
Abstract
4306 - Tumor Treating Fields (200 kHz) concomitant with weekly paclitaxel for platinum-resistant ovarian cancer: Phase 3 INNOVATE-3/ENGOT-ov50 study
Presenter: Ignace Vergote
Session: Poster Display session 2
Resources:
Abstract
5136 - Randomized, phase 1b/2 study of M6620 + avelumab + carboplatin vs standard care (sc) in patients (pts) with platinum-sensitive poly (ADP-ribose) polymerase inhibitor-(PARPi)-resistant ovarian cancer
Presenter: Susana Banerjee
Session: Poster Display session 2
Resources:
Abstract
2296 - An umbrella study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer: A Korean Gynecologic Oncology Group study (KGOG 3045), AMBITION
Presenter: Jung-Yun Lee
Session: Poster Display session 2
Resources:
Abstract
2732 - A phase 2 study of pembrolizumab in combination with doxorubicin in advanced, recurrent or metastatic endometrial cancer
Presenter: Ana Oaknin
Session: Poster Display session 2
Resources:
Abstract
4404 - ENGOT-EN9/LEAP-001: a phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer
Presenter: Christian Marth
Session: Poster Display session 2
Resources:
Abstract
4564 - Phase 1/2 trial of tisotumab vedotin plus bevacizumab, pembrolizumab, or carboplatin in recurrent or metastatic cervical cancer (innovaTV 205/ENGOT-cx8)
Presenter: Ignace Vergote
Session: Poster Display session 2
Resources:
Abstract
4933 - Updated data of Epitopes-HPV02 trial and external validation of efficacy of DCF in prospective Epitopes-HPV01 study in advanced anal squamous cell carcinoma. Pooled analysis of 115 patients
Presenter: Stefano Kim
Session: Poster Display session 2
Resources:
Abstract
2301 - Pre-specified pilot analysis of a randomised pilot/phase II/III trial comparing standard dose vs dose-escalated concurrent chemoradiotherapy (CRT) in anal cancer (PLATO-ACT5)
Presenter: Alexandra Gilbert
Session: Poster Display session 2
Resources:
Abstract