Spatial genomic heterogeneity in multiple myeloma revealed by multi-region sequencing

Area of Science:

• Oncology
• Genomics
• Cancer Biology

Background:

• Multiple myeloma involves malignant plasma cell expansion in the bone marrow.
• Rapid dissemination of aggressive clones is often anticipated due to bone marrow vascularity.
• Observed imbalanced distribution in medical imaging suggests complex spatial heterogeneity.

Purpose of the Study:

• To investigate the spatial clonal architecture of multiple myeloma.
• To understand the genomic heterogeneity within individual patients.
• To elucidate the evolutionary processes driving multiple myeloma progression.

Main Methods:

• Multi-region sequencing was performed on bone marrow and focal lesion specimens from 51 multiple myeloma patients.
• Specimens included iliac crest and radiology-guided focal lesions.
• Genomic analysis focused on identifying spatial clonal differences.

Main Results:

• Spatial genomic heterogeneity was detected in over 75% of patients.
• Common alterations included CDKN2C and TP53 inactivation, and MAPK pathway mutations.
• Increased spatial heterogeneity correlated positively with the size of biopsied focal lesions.

Conclusions:

• Multiple myeloma progression involves early clonal sweeps followed by regional evolution in advanced disease.
• Spatial heterogeneity is driven by the regional outgrowth of advanced clones.
• Multi-region investigations are essential for understanding intra-patient heterogeneity and myeloma evolution.