摘要：Esophageal cancer has a strikingly low survival rate mainly due to the lack of diagnostic markers for early detection and effective therapies. In the U.S., 75% of individuals diagnosed with esophageal squamous cell carcinoma (ESCC) are of African descent. African American ESCC (AA ESCC) is particularly aggressive, and its biological underpinnings remain poorly understood. We sought to identify the genomic abnormalities by conducting whole exome sequencing of 10 pairs of matched AA esophageal squamous cell tumor and control tissues. Genomic analysis revealed diverse somatic mutations, copy number alterations (SCNAs), and potential cancer driver genes. Exome variants created two subgroups carrying either a high or low tumor mutation burden. Somatic mutational analysis based on the Catalog of Somatic Mutations in Cancer (COSMIC) detected SBS16 as the prominent signature in the high mutation rate group suggesting increased DNA damage. SBS26 was also detected, suggesting possible defects in mismatch repair and microsatellite instability. We found SCNAs in multiple chromosome segments, encoding
MYC on 8q24.21,
PIK3CA and
SOX2 on 3q26,
CCND1,
SHANK2,
CTTN on 11q13.3, and
KRAS on 12p12. Amplifications of
EGFRvIII and
EGFRvIVa mutants were observed in two patients, representing a novel finding in ESCC that has potential clinical relevance. This present exome sequencing, which to our knowledge, represents the first comprehensive exome analysis exclusively in AA ESCC, and highlights novel mutated loci that might explain the aggressive nature of AA ESCC and lead to the development of diagnostic and prognostic markers as well as therapeutic targets.
