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Comprehensive Genomic Profiling of Rare Tumors: Routes to Targeted Therapies
Shuhang Wang1, Rongrong Chen2, Yu Tang1
1Clinical Cancer Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Abstract:
Comprehensive Genomic Profiling may be informative for novel treatment strategies and to improve outcomes for patients with rare tumors. This study aims to discover opportunities for use of targeted therapies already approved for routine use in patients with rare tumors. Solid tumors with an incidence lower than 2.5/100,000 per year was defined as rare tumors in China after comprehensive analysis based on epidemiological data and current availability of standardized treatment. Genomic data of rare tumors from the public database cBioPortal were compared with that of the Chinese population for targetable genomic alterations (TGAs). TGAs were defined as mutations of ALK, ATM, BRAF, BRCA1, BRCA2, CDKN2A, EGFR, ERBB2, FGFR1,2,3, KIT, MET, NF1, NTRK1,2,3, PIK3CA, PTEN, RET, and ROS1 with level 1 to 4 of evidence according to the OncoKB knowledge database. Genomic data of 4,901 patients covering 63 subtypes of rare tumor from cBioPortal were used as the western cohort. The Chinese cohort was comprised of next generation sequencing (NGS) data of 1,312 patients from across China covering 67 subtypes. Forty-one subtypes were common between the two cohorts. The accumulative prevalence of TGAs was 20.40% (1000/4901) in cBioPortal cohort, and 53.43% (701/1312) in Chinese cohort (p < 0.001). Among those 41 overlapping subtypes, it was still significantly higher in Chinese cohort compared with cBioPortal cohort (54.1%% vs. 26.1%, p < 0.001). Generally, targetable mutations in BRAF, BRCA2, CDKN2A, EGFR, ERBB2, KIT, MET, NF1, ROS1 were ≥3 times more frequent in Chinese cohort compared with that of the cBioPortal cohort. Cancer of unknown primary tumor type, gastrointestinal stromal tumor, gallbladder cancer, intrahepatic cholangiocarcinoma, and sarcomatoid carcinoma of the lung were the top 5 tumor types with the highest number of TGAs per tumor. The incidence of TGAs in rare tumors was substantial worldwide and was even higher in our Chinese rare tumor population. Comprehensive genomic profiling may offer novel treatment paradigms to address the limited options for patients with rare tumors.
Insights
Comprehensive genomic profiling reveals a high prevalence of targetable genomic alterations (TGAs) in rare tumors, particularly in the Chinese population. These findings support the use of targeted therapies for improved patient outcomes.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Rare tumors often present limited treatment options.
- Comprehensive genomic profiling (CGP) can identify actionable mutations.
- Targeted therapies offer potential treatment strategies for rare tumors.
Purpose of the Study:
- To identify targetable genomic alterations (TGAs) in rare tumors.
- To compare the prevalence of TGAs in Chinese and Western rare tumor populations.
- To explore opportunities for targeted therapy use in rare tumors.
Main Methods:
- Defined rare tumors in China based on incidence data.
- Utilized cBioPortal database for Western cohort genomic data.
- Analyzed next-generation sequencing (NGS) data from a Chinese cohort.
- Compared TGAs prevalence between cohorts for specific genes (e.g., ALK, BRAF, EGFR, MET, ROS1).
Main Results:
- The Chinese cohort showed a significantly higher prevalence of TGAs (53.43%) compared to the Western cohort (20.40%).
- TGAs were also more frequent in overlapping rare tumor subtypes between the cohorts (54.1% vs. 26.1%).
- Mutations in BRAF, BRCA2, CDKN2A, EGFR, ERBB2, KIT, MET, NF1, and ROS1 were at least three times more common in the Chinese cohort.
Conclusions:
- The incidence of TGAs in rare tumors is substantial globally and notably higher in the Chinese population.
- CGP is crucial for identifying treatment opportunities in rare tumors.
- Findings support the development of novel treatment paradigms for rare tumors using targeted therapies.
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