There is increasing recognition that diverse populations should be included in cancer genomics and epigenomics studies to identify differences within these populations that might account for disparities in cancer incidence and survival. To date, much of our knowledge of the genetic features of cancer comes from analysis of samples from The Cancer Genome Atlas (TCGA), which mostly comprises tumours derived from patients with European ancestry. To address this shortcoming, Sinha et al. set about systematically mapping genomic alterations in lung tumours from an ethnically unbiased patient cohort.

Credit: Lara Crow/Springer Nature Limited

Using 222 lung tumour samples from the National Cancer Institute-Maryland (NCI-MD) study, the researchers produced genome-wide copy-number profiles. This revealed that lung squamous cell carcinomas (LUSCs) but not lung adenocarcinomas (LUADs) from African Americans (AAs) had higher genomic instability (GI) than European Americans (EAs). Likely accounting for this difference in GI in LUSCs was a higher degree of homologous recombination deficiency (HRD). Furthermore, complex structural variants associated with HRD, such as chromothripsis, were more common in LUSCs from AAs than EAs and to a lesser extent in LUADs.

Probing the differences in somatic copy-number alterations (SCNAs) in more detail revealed that lung cancer subtype-specific SCNAs at the level of the chromosome arm were detected at a higher frequency in tumours from AAs than EAs. Furthermore, eight novel AA-specific focal-level — defined as shorter than half a chromosome arm — SCNAs were identified. Recurrent features at the gene level included KRAS amplification and PTEN deletion occurring more often in LUSCs from AAs than EAs.

calls for more studies powered to compare differences by ancestry groups

Importantly, observations made within the NCI-MD cohort were validated with analysis of TCGA, despite the relatively small number of samples from AAs in this cohort. Extending their analysis to more cancer types by mining TCGA SCNA profiles of 6,492 pan-cancer samples showed a general trend for higher levels of GI, HRD and chromothripsis across multiple tumour types from AAs. The increased germline HRD noted in the pan-cancer samples and LUSCs from AAs might underlie these somatic differences.

This work calls for more studies powered to compare differences by ancestry groups to help reduce worldwide cancer burden.