Mobile element insertions and associated structural variants in longitudinal breast cancer samples

Area of Science:

• Genomics
• Cancer Biology
• Molecular Oncology

Background:

• Mobile elements are generally inactive in healthy tissues but show increased activity in cancers.
• Mobile elements contribute to genomic structural variations beyond simple insertion events.

Purpose of the Study:

• To investigate the timing and impact of mobile element insertions and associated structural variants in cancer.
• To analyze longitudinal samples from metastatic breast cancer patients to understand variant activity during tumor progression.

Main Methods:

• Analysis of longitudinal samples from four metastatic breast cancer patients.
• Identification and characterization of mobile element insertions and structural variants.

Main Results:

• Identified 11 mobile element insertions or associated structural variants.
• Found that the majority of these variants occurred early in tumor progression.
• Discovered a translocation interrupting MAP2K4 involving Alu elements and a deletion in YTHDF2, potentially inactivating tumor suppressor genes.

Conclusions:

• Most identified variants were likely passenger mutations, but some significantly impacted tumor progression.
• A MAP2K4-interrupting translocation is a potential driver mutation due to its high variant allele fraction and gene's known function.
• Mobile elements play a role in generating potentially oncogenic structural variants during cancer development.