Comprehensive analysis of targetable mutations and tumor microenvironment in urachal cancer
David J Benjamin1, Tolulope T Adeyelu2, Andrew Elliott2
1Hoag Family Cancer Institute, Newport Beach, CA, 92663, USA. David.Benjamin@hoag.org.
Abstract:
Urachal cancer, a rare malignancy, generally presents in the clinical setting with advanced stages of disease. Systemic treatment with chemotherapy is generally utilized in this setting. However, there remains a paucity of data on the effectiveness of immune checkpoint inhibitors or targeted therapies for urachal cancer. We analyzed the genomic profile of urachal cancer in order to identify potentially targetable mutations and evaluate the tumor microenvironment. 42 urachal samples were retrospectively analyzed. Our results showed that TP53, GNAS and KRAS mutations were common in urachal cancer with increased prevalence of TP53 mutation in urachal cohorts without MAPK-alterations. The tumor microenvironment demonstrated increased NK cells in MAPK-altered urachal cancer. Finally, we show that urachal cancer shares genomic and transcriptomic similarity with colorectal cancer compared to bladder cancer. This study provides new insights into the molecular profiles of urachal tumor samples and possibility of association with colorectal cancer that might guide future clinical trial design.
Insights
This study reveals common TP53, GNAS, and KRAS mutations in urachal cancer, a rare cancer. Urachal tumors show similarities to colorectal cancer, potentially guiding future treatments.
Area of Science:
- Oncology
- Genomics
- Cancer Research
Background:
- Urachal cancer is a rare malignancy often diagnosed at advanced stages.
- Current systemic treatments primarily involve chemotherapy, with limited data on targeted therapies or immune checkpoint inhibitors.
- Understanding the molecular landscape of urachal cancer is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To analyze the genomic profile of urachal cancer to identify targetable mutations.
- To evaluate the tumor microenvironment in urachal cancer.
- To compare the molecular characteristics of urachal cancer with other malignancies.
Main Methods:
- Retrospective analysis of genomic profiles from 42 urachal cancer samples.
- Identification of common mutations, including TP53, GNAS, and KRAS.
- Assessment of tumor microenvironment, including immune cell populations.
Main Results:
- TP53, GNAS, and KRAS mutations were frequently observed in urachal cancer.
- TP53 mutations were more prevalent in urachal cohorts lacking MAPK alterations.
- Increased natural killer (NK) cells were noted in the tumor microenvironment of MAPK-altered urachal cancer.
- Genomic and transcriptomic analyses indicated similarities between urachal cancer and colorectal cancer, distinct from bladder cancer.
Conclusions:
- Urachal cancer exhibits specific common mutations (TP53, GNAS, KRAS) and a distinct tumor microenvironment.
- The observed molecular similarities between urachal cancer and colorectal cancer suggest potential shared therapeutic targets.
- These findings may inform the design of future clinical trials for urachal cancer, possibly leveraging insights from colorectal cancer treatment.
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