[A Case of Lynch Syndrome with MLH1 Gene Mutation Identified by Comprehensive Genomic Profiling]

Area of Science:

• Oncology
• Genetics
• Genomic Medicine

Background:

• A patient in her 60s presented with a positive fecal occult blood test, leading to the discovery of multiple advanced colorectal cancers.
• Initial treatment involved subtotal colectomy and adjuvant chemotherapy (CAPOX regimen).

Purpose of the Study:

• To highlight the importance of considering hereditary cancer syndromes in patients with multiple malignancies.
• To showcase the clinical utility of comprehensive genomic profiling and genomic medicine in guiding treatment decisions.

Main Methods:

• Colonoscopy revealed multiple advanced colorectal cancers.
• Subtotal colectomy and CAPOX chemotherapy were administered.
• Comprehensive genomic profiling (CGP) and next-generation sequencing (NGS) identified an MLH1 pathogenic variant, diagnosing Lynch syndrome.
• Treatment with ipilimumab plus nivolumab, followed by nivolumab monotherapy, was initiated for metastatic disease.

Main Results:

• Metastases to the lungs and mediastinal lymph nodes were observed 10 months post-surgery.
• Treatment with immune checkpoint inhibitors resulted in sustained tumor shrinkage.
• The patient remained disease-free with no new malignancies or recurrence for over 4 years post-surgery.

Conclusions:

• Early consideration of hereditary tumors, such as Lynch syndrome, is crucial in patients with multiple primary cancers and relevant family history.
• Genomic medicine, including CGP and NGS, plays a vital role in accurate diagnosis and personalized treatment strategies.
• Immunotherapy demonstrated significant efficacy in managing metastatic colorectal cancer associated with Lynch syndrome.