Scientists from the Cancer Genome Atlas have published the first comprehensive catalogue of genetic alterations found in 279 squamous cell carcinoma of the head and neck, and have identified several disrupted molecular pathways that might be targeted by existing and future anticancer drugs.
According to the study authors, the findings should help in developing targeted therapies and bringing the methods of precision cancer medicine to these cancers, which impact about 600,000 patients a year worldwide. The article is to be published in the journal Nature.
Head and neck cancers are the latest type of cancer to be profiled by scientists in the Cancer Genome Atlas Network. The genome atlas project's goal is to study more than 10,000 human tumours at the molecular level to understand the biological causes of cancer and discover new targets for precision drug therapies.
The team analysed the results of the research carried out on each of the 279 tumour specimens to look for altered genes, gains or losses of parts of chromosomes, variations in the numbers of copies of genes present in the tumour DNA, and other changes making up the genomic landscape of the head and neck squamous cell carcinomas.
Traditionally, most cancers of the head and neck have been linked to longtime heavy alcohol consumption and smoking. But increasingly, these cancers are being diagnosed in people who are infected with the human papilloma virus (HPV); these patients tend to have better outcomes and have different characteristics than those caused by alcohol and tobacco.
The new study found that tumours from HPV-infected patients were different in numerous ways from those related to smoking and drinking, with different disrupted cellular pathways and gene alterations. HPV-associated tumours are dominated by PIK3CA mutations, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1.
Smoking-related head and neck squamous cell carcinomas demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22.
A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53.
Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours.
Therapeutic candidate alterations were identified in most head and neck squamous cell carcinomas.
This study was supported by USA National Institutes of Health grants.
Reference
Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015; 517(7536):576-82. doi: 10.1038/nature14129.