Common anti-cancer therapies induce somatic mutations in stem cells of healthy tissue

Area of Science:

• Oncology
• Genetics
• Stem Cell Biology

Background:

• Genome-wide mutation analyses identify anti-cancer drugs mutagenic to cancer cells.
• The impact of these therapies on normal cells remains largely unknown.
• Adult stem cells (ASCs) are crucial for tissue renewal and long-term health.

Purpose of the Study:

• To investigate the genome-wide somatic mutation patterns in healthy colon and liver ASCs from cancer patients.
• To determine the mutagenic effects of systemic chemotherapy and/or local radiotherapy on normal stem cells.

Main Methods:

• Analysis of genome-wide somatic mutations in 42 healthy ASCs (colon or liver) from 14 cancer patients.
• Patients received systemic chemotherapy (Oxaliplatin, 5-FU) and/or local radiotherapy.
• Comparison of mutation frequencies between colon and liver ASCs.

Main Results:

• Oxaliplatin induced an average of 535 mutations in colon ASCs.
• 5-Fluorouracil (5-FU) showed minimal mutagenic effects in most colon ASCs.
• Normal liver ASCs demonstrated resistance to mutagenesis from Oxaliplatin and 5-FU.

Conclusions:

• Systemic cancer chemotherapies increase the mutational burden in long-lived normal stem cells.
• This increased mutational load in stem cells may elevate the risk of secondary cancers.
• Understanding therapy-induced mutagenesis in normal tissues is critical for long-term cancer patient care.