113P - Molecular profiling of biliary tract cancers in patients of African and European ancestries

Background

Molecular differences between genetic ancestries in patients (pts) with bilary tract cancers (BTCs) and how they affect prognosis and treatment response are largely unknown. Compounding this problem is clinical trial enrollment for racial minorities with BTCs have been historically low, making it difficult to assess differences in treatment response between genetic ancestries. Our prior data indicated significant variation in somatic cancer genes between Caucasian and Asian pts. However, variations in African ancestry (AA) pts have not been described.

Methods

12,932 cases of BTCs of AA and European ancestries (EA) were reviewed from 3 databases (Foundation Medicine (n=10,849), MD Anderson Cancer Center (n=167) and AACR Genie (n=1,916). BTCs were divided into intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinomas and gallbladder cancers (GBC). Prevalence of alterations in 30 genes between genetic ancestries were compared using Fischer’s exact test on the Foundation Medicine database. P-values were corrected for false discovery rate using the Benjamini/Hochberg adjustment.

Results

We identified key clinical and genomic differences between AA and EA BTC cases in all 3 databases. The mean age of AA pts at diagnosis was earlier (62.3 years) compared to EA pts (65.1 years) (p<0.05). There was a higher percent of female AA BTC cases (63.2%) compared to female EA BTC cases (52.4%) (p<0.05). AA BTC cases had a statistically significant higher prevalence of TP53 (55.1% vs 39.7%) and TERT (10.0% vs 5.4%) alterations (p<0.001) compared to EA BTC cases. AA BTC cases also had a statistically significant higher prevalence of STK11, CCNE, ERBB2, and ARID2 alterations (p<0.05), and lower prevalence of IDH1, ARID1A, BAP1, BRAF, and PBRM1 alterations (p<0.05) compared to EA BTC cases. AA ICC cases had a statistically significant higher prevalence of FGFR2 (16.8% vs 11.7%) alterations (p<0.001) compared to EA ICC cases.

Conclusions

Our results highlight significant differences in genomic profiles among BTC cases of different genetic ancestries and support further research in how these differences contribute to prognosis and treatment response to targeted therapies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

D.C. Pavlick: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine. J.S. Ross: Financial Interests, Personal, Full or part-time Employment, Medical Director: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Roche Holdings, Tango Therapeutics, Celsius Therapeutics. All other authors have declared no conflicts of interest.