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.
Highlights
Molecular profiling to identify potential therapeutic targets has been widely applied in common tumors such as lung cancer [1, 2], breast cancer [3, 4], melanoma [5], and colorectal cancer [6, 7]
Rare tumors according to our China-specific definition included 141 tumor types
We analyzed a total of 45,666 samples from the cBioPortal database and identified 4,901 samples of rare tumors that matched our definition, representing 63 of the 141 possible tumor types
Summary
Molecular profiling to identify potential therapeutic targets has been widely applied in common tumors such as lung cancer [1, 2], breast cancer [3, 4], melanoma [5], and colorectal cancer [6, 7]. Limited information is available regarding the utility of targeted therapy for rare tumors [10, 11]. There is no universally applied definition for rare tumors (Table 1). The National Cancer Institute (NCI) (https://www.cancer.gov/publications/dictionaries/cancerterms/def/791790) and Food and Drug Administration (FDA) (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789814/) defines it as a tumor with an annual incidence of
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