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Genomic Profiling of KRAS/NRAS/BRAF/PIK3CA Wild-Type Metastatic Colorectal Cancer Patients Reveals Novel Mutations in Genes Potentially Associated with Resistance to Anti-EGFR Agents

Authors
  • rachiglio, anna maria
  • lambiase, matilde
  • fenizia, francesca
  • roma, cristin
  • cardone, claudia
  • iannaccone, alessia
  • de luca, antonella
  • carotenuto, marianeve
  • frezzetti, daniela
  • martinelli, erika
  • maiello, evaristo
  • ciardiello, fortunato
  • normanno, nicola
Publication Date
Jun 20, 2019
Source
MDPI
Keywords
Language
English
License
Green
External links

Abstract

(CAPRI-GOIM) trial of first line FOLFIRI plus cetuximab. Tumor samples were analyzed with a targeted sequencing panel covering single nucleotide variants (SNVs), insertions/deletions (Indels), copy number variations (CNVs), and gene fusions in 143 cancer-related genes. The analysis revealed in all 21 patients the presence of at least one SNV/Indel and in 10/21 cases (48%) the presence of at least one CNV. Furthermore, 17/21 (81%) patients had co-existing SNVs/Indels in different genes. Quadruple-wt mCRC from patients with the shorter progression free survival (PFS) were enriched with peculiar genetic alterations in KRAS, FBXW7, MAP2K1, and NF1 genes as compared with patients with longer PFS. These data suggest that a wide genetic profiling of quadruple-wt mCRC patients might help to identify novel markers of de novo resistance to anti-EGFR MoAbs.

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