Mutational Status of CDKN2A and TP53 Genes in Laryngeal Squamous Cell Carcinoma

Abstract

Laryngeal squamous cell carcinoma (LSCC) is the second most common tumour of the head and neck. It is characterized by frequent aberrations in two cell-cycle regulators--CDKN2A and TP53. However, LSCC has been often studied as a part of the group of head and neck cancers and not as an individual entity. In the current study we aimed to examine mutation status of CDKN2A and TP53 genes in 108 LSCC patients. DNA was extracted from fresh-frozen tumour tissues; exons 1-3 of CDKN2A and exons 5-8 of TP53 were screened for mutations by direct sequencing. Genetic aberrations in CDKN2A were found in 16 (14.2%) and those in TP53--in 56/108 (51.9%) tumours. Seven mutations (two insertions, three deletions, one missense and one silent) detected in CDKN2A were not described previously. Also, we found seven novel deletions and a novel indel in TP53. No significant associations with clinical features were found. However, TP53 mutations were predominantly observed in smokers with advanced stage tumours. Screening for genetic aberrations in a defined group of LSCC contributes to the knowledge about laryngeal carcinogenesis. Further investigations are required to confirm the observed trends in associations with clinical features.

<p>Novel genetic alterations and their impact on target therapy response in head and neck squamous cell carcinoma</p>

“…Maintenance of cyclin D1 levels is critical to the resistance HNSCC cells display to gefitinib 54. Sensitivity of the six HNSCC cell lines (FaDu, Detroit 562, SCC 9, SCC 15, SCC 25, and CAL 27) to gefitinib was related to cyclin D1 overexpression.…”

“…It is thought to be involved in early stages of HNSCC development. It is affected in up to 80% of HNSCC – often deleted, hyper-methylated, or, much rarely, mutated 42. CDKN2A mutation is considered as “noncoding mutations”, “inactivation”, or “loss of function” 43.…”

“…It is associated with worse oversurvival in patients with recurrent and metastatic HNSCC (MSKCC, JAMA Oncol 2016) (Figure 4). 13 Most of the mutations in CDKN2A were found in exon 2 of the gene 42. However, these are likely insufficient to drive tumorigenesis by CDKN2A mutations themselves 44.…”

“…HPV-positive HNSCC rarely has CDKN2A mutation and thus has the p16INK4a function;26,54 those patients are significantly less likely to develop a locoregional recurrence 43. On the other hand, up to 90% of HPV-negative HNSCCs have loss of p16INK4a function as a result of CDKN2A mutation, promoter methylation, or gene/chromosome 9p21 deletion 45.…”

LncRNA MEG3 inhibits cell proliferation and induces apoptosis in laryngeal cancer via miR‐23a/APAF‐1 axis

“…Moreover, some researchers have found that people with a family history of cancer are also susceptible to laryngeal cancer, which implicates that genetic factors serve an important role in the occurrence and progression of laryngeal cancer . Growing evidence has demonstrated that some tumour suppressor genes, such as CDKN2A, TP53 and CTNNA2, are down‐regulated or inactivated in laryngeal cancer tissues and contributed to the tumorigenesis of laryngeal cancer . Recent studies have found that long non‐coding RNAs (LncRNAs), a member of non‐coding RNA gene family, are dysregulated in laryngeal cancer tissues .…”