Longitudinal analysis of 25 sequential sample-pairs using a custom multiple myeloma mutation sequencing panel (M(3)P)

Area of Science:

• Genomics
• Oncology
• Molecular Biology

Background:

• Next-generation sequencing (NGS) advances enable rapid clinical results for personalized cancer treatment.
• No established gene panel exists for multiple myeloma (MM)-specific genomic profiling.

Purpose of the Study:

• To design and validate a novel 47-gene targeted sequencing panel for multiple myeloma.
• To analyze tumor/germline DNA in MM patients longitudinally to track clonal evolution.

Main Methods:

• Designed a 47-gene panel (39 common MM mutations, 8 targeted pathway genes).
• Performed targeted sequencing on tumor/germline DNA from 25 MM patients with pre- and post-treatment samples.

Main Results:

• KRAS (36%), NRAS (20%), TP53 (16%), DIS3 (16%), FAM46C (12%), and SP140 (12%) were most frequently mutated.
• Tracked clonal evolution, noting mutation changes in FAM46C, FAT1, KRAS, NRAS, SPEN, PRDM1, NEB, and TP53.
• Identified XBP1 mutations linked to bortezomib resistance.

Conclusions:

• The developed MM-specific gene panel enables individual tumor characterization.
• This panel facilitates longitudinal tracking of clonal evolution in multiple myeloma.
• Findings support the use of targeted sequencing for personalized MM treatment and monitoring.