Mutations of ARID1B, PIK3C2B, KMT2B, and FAT1 genes influence clinical outcome in newly diagnosed myeloma

Cancer Genet. 2024 Nov:288-289:118-125. doi: 10.1016/j.cancergen.2024.11.001. Epub 2024 Nov 6.

Abstract

The study aimed to elucidate the mutational profile of patients with newly diagnosed multiple myeloma to understand correlations of alterations with clinical outcomes. A cohort of 20 patients was enrolled, and mutational analysis was conducted using the TruSight Oncology 500 DNA Kit. Identified genetic alterations were related to clinicopathologic features and treatment outcomes. A total of 724 high-quality variants were validated. All patients harbored mutations associated with the RTK-RAS pathway, with over half having alterations in PI3 K, NOTCH, and WNT pathways. Several gene mutations were associated with specific clinical characteristics and prognostic indicators, revealing a complex interplay between genetic alterations and myeloma type, standard prognostic indicators, biochemical parameters, and renal function. Genetic alterations significantly influencing progression-free survival concerned PIK3C2B, ARID1B genes, and concomitant mutations in KMT2B, FAT1, and ARID1B. The findings underscore the potential of gene mutation-based prognostic tools in enhancing clinical decision-making and suggest that further exploration of identified genetic markers could pave the way for improved prognostic stratification and targeted therapeutic interventions in multiple myeloma.

Keywords: ARID1B; FAT1; KMT2B; Multiple myeloma; Next-generation sequencing; PIK3C2B; Prognosis.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Cadherins
  • DNA-Binding Proteins* / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma* / genetics
  • Mutation*
  • Neoplasm Proteins
  • Prognosis
  • Transcription Factors* / genetics

Substances

  • DNA-Binding Proteins
  • Transcription Factors
  • FAT1 protein, human
  • ARID1B protein, human
  • KMT2D protein, human
  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Cadherins