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Precision oncology for gallbladder cancer: insights from genetic alterations and clinical practice
Jianzhen Lin1, Kun Dong2, Yi Bai1
1Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing 100730, China.
Background:
Gallbladder cancer (GBC) is an uncommon but highly fatal malignancy, with limited adjuvant therapy. The present study aims to explore the actionable alterations and precision oncology for GBC patients.
Methods:
Patients with pathologically confirmed GBC who progressed after first-line systemic treatment were enrolled. Genomic alterations were captured by ultra-deep targeted next-generation sequencing (tNGS). The actionabilities of alterations and the therapeutic regimens were evaluated by a multidisciplinary tumor board (MDTB).
Results:
Sixty patients with GBC were enrolled and analyzed. tNGS was successfully achieved in all patients. The median tumor mutation burden for GBC patients was 5.4 (range: 0.8-36.74) mutations/Mb, and the most common mutations were in TP53 (73%), CDKN2A (25%) and PIK3CA (20%). The most frequently copy-number altered genes were CDKN2A deletion (11.7%) and ERBB2 amplification (13.3%). 23% of the patients displayed gene fusion; 17 fusion events were identified, and 14 of the 17 fusion events co-occurred with mutations in driver genes. In total, 46 of the 60 (76%) patients were identified as possessing at least one actionable target to proceed precision oncology.
Conclusions:
The present study revealed the mutational profile for the clinical practice of precision oncology in GBC patients.
Insights
This study identifies actionable genomic alterations in gallbladder cancer (GBC) using targeted next-generation sequencing. Results support precision oncology approaches for GBC patients, improving treatment strategies.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Gallbladder cancer (GBC) is a rare but aggressive malignancy with limited treatment options.
- There is a need to identify new therapeutic targets for GBC.
Purpose of the Study:
- To explore actionable genomic alterations in GBC patients.
- To evaluate the potential for precision oncology in GBC treatment.
Main Methods:
- Ultra-deep targeted next-generation sequencing (tNGS) was used to analyze genomic alterations in GBC patients.
- A multidisciplinary tumor board (MDTB) assessed the actionability of identified alterations and therapeutic regimens.
- Sixty GBC patients who progressed after first-line treatment were enrolled.
Main Results:
- tNGS successfully identified genomic alterations in all patients.
- Common mutations included TP53 (73%), CDKN2A (25%), and PIK3CA (20%).
- CDKN2A deletion (11.7%) and ERBB2 amplification (13.3%) were frequent copy-number alterations.
- Gene fusions were observed in 23% of patients, often co-occurring with driver gene mutations.
- 76% of patients had at least one actionable target for precision oncology.
Conclusions:
- This study provides a comprehensive mutational profile for GBC.
- The findings support the clinical application of precision oncology in GBC management.
- Identifying actionable targets can guide personalized treatment strategies for GBC patients.
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