DNA-Repair Gene Mutations Are Highly Prevalent in Circulating Tumour DNA from Multiple Myeloma Patients
Autor: | Malarmathy Ramachandran, Kawa Choi, John V. Reynolds, Sridurga Mithraprabhu, Tiffany Khong, Daniela Klarica, Andrew Spencer, Jay Hocking |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Cancer Research medicine.medical_specialty DNA repair Biology medicine.disease_cause lcsh:RC254-282 Article DNA-repair genes 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine TP53 Liquid biopsy Gene Multiple myeloma Hematology liquid biopsy circulating tumour DNA medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Molecular biology multiple myeloma 030104 developmental biology medicine.anatomical_structure Oncology chemistry 030220 oncology & carcinogenesis haematology Bone marrow KRAS prognosis DNA RAS |
Zdroj: | Cancers Cancers, Vol 11, Iss 7, p 917 (2019) Volume 11 Issue 7 |
ISSN: | 2072-6694 |
Popis: | Mutational characterisation utilising plasma (PL)-derived circulating tumour DNA (ctDNA) in multiple myeloma (MM) has been recently described. Mutational analyses of paired bone marrow (BM) MM cell DNA and ctDNA from 76 patients (n = 24, new diagnosis (ND), n = 52, relapsed/refractory (RR)) for (ras/raf signaling pathway) and tumour protein p53 (TP53) mutations using the OnTarget&trade Mutation Detection (OMD) platform was performed. The total number and proportions of mutations in each of the compartments (BM-specific, PL-specific or shared) was significantly higher in RR patients compared to ND patients (p = 0.0002 and p < 0.0001, respectively). Patients with > 2 mutations or > 1% fractional abundance (FA) in the PL had significantly shorter overall survival (OS) (p = 0.04 and p = 0.0006, respectively). Patients with PL-specific TP53 mutations had significantly shorter OS compared to patients with no PL-TP53 mutations (p = 0.003), while no differences were observed in patients with (K-ras) KRAS mutations. Targeted deep amplicon sequencing (TAS) of matched PL and BM samples from 36 MM patients for DNA-repair and RAS-RAF pathway genes found that DNA-repair genes were present at significantly higher levels in the PL when compared to RAS-RAF mutations (p = 0.0095). We conclude that ctDNA analysis identifies a higher prevalence of potentially actionable DNA-repair gene mutated subclones than BM analysis. |
Databáze: | OpenAIRE |
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