Islands of genomic stability in the face of genetically unstable metastatic cancer.

ABSTRACT:

Introduction

Metastatic cancer affects millions of people worldwide annually and is the leading cause of cancer-related deaths. Most patients with metastatic disease are not eligible for surgical resection, and current therapeutic regimens have varying success rates, some with 5-year survival rates below 5%. Here we test the hypothesis that metastatic cancer can be genetically targeted by exploiting single base substitution mutations unique to individual cells that occur as part of normal aging prior to transformation. These mutations are targetable because ~10% of them form novel tumor-specific "NGG" protospacer adjacent motif (PAM) sites targetable by CRISPR-Cas9.

Methods

Whole genome sequencing was performed on five rapid autopsy cases of patient-matched primary tumor, no

SUBMITTER: Bowland K 

PROVIDER: S-EPMC10862738 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature