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Poster Display session 2

3182 - Clonal hematopoiesis mutations in plasma cfDNA RAS/BRAF genotyping of metastatic colorectal cancer


29 Sep 2019


Poster Display session 2


Tumour Site

Colon and Rectal Cancer


Beili Wang


Annals of Oncology (2019) 30 (suppl_5): v198-v252. 10.1093/annonc/mdz246


B. Wang1, F. Huang1, M. Shen1, S. Wu1, H. Wang1, H. Jiang1, Y. Yu2, Q. Yu1, Y. Yang1, Y. Zhao1, Y. Zhou1, B. Pan1, T. Liu2, W. Guo1

Author affiliations

  • 1 Laboratory Medicine, Zhongshan Hospital, Fudan University, 200032 - Shanghai/CN
  • 2 Medical Oncology, Zhongshan Hospital, Fudan University, 200032 - Shanghai/CN


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Abstract 3182


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.


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.


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.


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.


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).


All authors have declared no conflicts of interest.

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