Roepman et al. (2005) showed that DNA microarray gene expression profiling can detect lymph node metastases for primary head and neck squamous cell carcinomas that arise in the oral cavity and oropharnyx. The predictor, established with a set ... Roepman et al. (2005) showed that DNA microarray gene expression profiling can detect lymph node metastases for primary head and neck squamous cell carcinomas that arise in the oral cavity and oropharnyx. The predictor, established with a set of 82 tumors, outperformed current clinical diagnosis when independently validated. The 102 predictor genes offered unique insight into the processes underlying metastasis. The results showed that the metastatic state can be deciphered from the primary tumor gene expression pattern and that treatment can be substantially improved.
Pai et al. (1998) performed sequence analysis of all 10 coding exons of the TNFRSF10B gene (603612.0001) in 20 primary head and neck cancers with allelic loss of 8p. To ... - Mutation in the TNFRSF10B Gene Pai et al. (1998) performed sequence analysis of all 10 coding exons of the TNFRSF10B gene (603612.0001) in 20 primary head and neck cancers with allelic loss of 8p. To screen for a subset of mutations localized to the functional cytoplasmic death domain, they sequenced this region in an additional 40 primary head and neck cancers. They found 2 alterations, including a 2-bp insertion at a minimal repeat site (603612.0001), introducing a premature stop codon and resulting in a truncated protein. Sequence analysis of normal tissue from the patient showed that the truncating mutation was also present in the germline, and that the tumor did not have a p53 mutation. - Mutation in the ING1 Gene In tumor tissue of squamous cell carcinoma of the head and neck, Gunduz et al. (2000) identified missense mutations in the ING1 gene (see, for example, 601566.0001). - Mutation in the PTEN Gene In a study of 52 HNSCC tumor samples, Poetsch et al. (2002) found an ala121-to-gly mutation (A121G; 601728.0031) in the PTEN gene in 1 oropharyngeal and 1 laryngeal carcinoma. - Role of MicroRNAs Cervigne et al. (2009) examined microRNA (miR) expression changes in 43 sequential progressive oral leukoplakia samples from 12 patients and 4 nonprogressive leukoplakias from 4 different patients. The findings were validated using quantitative RT-PCR in an independent cohort of 52 progressive dysplasias and oral squamous cell carcinomas (OSCCs), and 5 nonprogressive dysplasias. Global miR expression profiles distinguished progressive leukoplakia/OSCC from nonprogressive leukoplakias/normal tissues. Of 109 miRs which were highly expressed exclusively in progressive leukoplakia and invasive OSCC, miR21 (611020), miR181b (612744), and miR345 expression was consistently increased and associated with increases in lesion severity during progression. The authors hypothesized that overexpression of miR21, miR181b, and miR345 may play an important role in malignant transformation. - Mutation in Genes Involved in Squamous Differentiation To explore the genetic origins of head and neck squamous cell carcinoma, Agrawal et al. (2011) used whole-exome sequencing and gene copy number analyses to study 32 primary tumors. Tumors from patients with a history of tobacco use had more mutations than did tumors from patients who did not use tobacco, and tumors that were negative for human papillomavirus (HPV) had more mutations than did HPV-positive tumors. Six of the genes that were mutated in multiple tumors were assessed in up to 88 additional HNSCCs. In addition to previously described mutations in TP53, CDKN2A, PIK3CA (171834), and HRAS (171834), Agrawal et al. (2011) identified mutations in NOTCH1 (190198). Nearly 40% of the 28 mutations identified in NOTCH1 were predicted to truncate the gene product, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type. Seven of 21 patients with NOTCH1 mutations had 2 independent mutations presumably on different alleles. After TP53, NOTCH1 was the most frequently mutated gene found in the combined discovery and prevalence sets, with alterations present in 15% of patients. Stransky et al. (2011) independently analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying known HNSCC genes, their analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (i.e., NOTCH1; IRF6, 607199; and TP63, 603273), implicating its dysregulation as a major driver of HNSCC carcinogenesis. - Mutation in the FBXW7 Gene Among 120 primary HNSCCs, Agrawal et al. (2011) identified 6 mutations in FBXW7. Two were indels and the other 4 were missense; none was homozygous. The FBXW7 mutations observed were in a hotspot known to block the degradation of active NOTCH1. Agrawal et al. (2011) noted that FBXW7 mutations had not been observed in HNSCC, although they are frequent in other tumor types.