In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13144-e13144
Abstract:
e13144 Background: More than 50% of solid cancers sooner or later escape control of standard treatments. Detection and analysis of cell free circulating DNA (cfDNA) now offer the possibility to detect key mutations of cancer driver genes which may play a major role in the therapy escaping mechanism. We sought to identify clones of solid tumors escaping standard treatments in order to assess personalized treatment at PD. Methods: A cohort of patients with 10 different solid tumors progressing after standard therapy were selected. CfDNA analysis was performed using PAXgene blood ccfDNA tubes (QIAGEN), MagMAX cell-free total nucleic acid isolation kit, and ION PROTON platform (ThermoFisher Scientific). Results: Next generation sequencing analysis of 52 cancer-driver genes of cfDNA samples of 39 patients allowed for picking up clones plausibly involved in the PD mechanism in 60% of cases. A mean of 1.3 mutated genes (range 1-3) for each tumor was found. Point mutations in TP53, PIK3CA, and CNV in FGFR3 were the most commonly observed, with a rate of 41%, 16%, and 13%, respectively. Increased copy number variations of FGF receptors were identified in patients with non-small cell lung, pancreatic, and gastric cancer, and cholangiocarcinoma. Other clones had mutations in ESR1 (breast), CTNNB1 (uterus), KRAS and CCND2 (pancreas), EGFR and BRAF (lung). Interestingly, retinoblastomas resistant to Melphalan showed expanding mutated clones in PTEN or SMAD4. Increased levels of cfDNA were observed in the plasma of all patients. Conclusions: The results presented here show that irrespective of the primary tumor mutational burden and subsequent complex clonal evolution, a simplified mutational load is present at PD. One or few “sniper” clones drive progression and the molecular profile has a weak correlation with the primary tumor. Single driver mutations in TP53 remain the main target of a not yet developed specific therapy in most tumors such as breast, ovarian, uterine, lung, gastric cancers and glioblastoma. Among the actionable mutations, PIK3CA were found, not only in breast cancers, but also in uterine carcinoma, Sezary syndrome and glioblastoma, pinpointing the needs of specific trials in these tumors.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.15_suppl.e13144
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2019
detail.hit.zdb_id:
2005181-5
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