Molecular Detection of Early-Stage Laryngopharyngeal Squamous Cell Carcinomas

Temam, Stéphane; Bénard, Jean; Dugas, Christelle; Trassard, Martine; Gormally, Emmanuelle; Soria, Jean‐Charles; Faivre, Sandrine; Luboinski, B.; Marandas, P.; Hainaut, Pierre; Lenoir, Gilbert; Li, Mao; Janot, F.

doi:10.1158/1078-0432.ccr-04-1535

Cited by 13 publications

(15 citation statements)

References 17 publications

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“…This setup reduces sample handling and thus the risk of PCR contamination. In previous studies, 25-50% of HNSCCs showed abnormalities in D7S1482 (Coulet et al, 2000;Temam et al, 2005). In one of these studies, the majority of the mutations observed were insertion mutations (Coulet et al, 2000).…”

Section: Discussionmentioning

confidence: 91%

Microsatellite mutations in buccal cells are associated with aging and head and neck carcinoma

Slebos

Vadivelu

et al. 2008

Br J Cancer

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Carcinogen exposure from tobacco smoking is the major cause of upper aerodigestive tract cancer, yet heavy smokers only have about a 10% life-time risk of developing one of these cancers. Current technologies allow only limited prediction of cancer risk and there are no approved screening methods applicable to the general population. We developed a method to assess somatic mutational load using small-pool PCR (SP-PCR) and analysed mutations in DNA isolated from cells obtained by mouth rinse. Mutation levels in the hypermutable tetranucleotide marker D7S1482 were analysed in specimens from 25 head and neck squamous carcinoma (HNSCC) cases and 31 controls and tested for associations with age, smoking history and cancer status. We found a significant association between mutation frequency and age (P ¼ 0.021, Generalized Linear Model (GLM), N ¼ 56), but no influence of smoking history. Cases had higher mutation frequencies than controls when corrected for the effects of age, a difference that was statistically significant in the subgroup of 10 HNSCC patients who were treated with surgery only (P ¼ 0.017, GLM, N ¼ 41). We also present evidence that cancer status is linked to levels of nonunique, and presumably clonally derived, mutations in D7S1482. Insertion mutations were observed in 833 (79%) of 1058 alleles, of which 457 (43%) could be explained by insertion of a single repeat unit; deletion mutations were found in 225 (21%) of tested alleles.In conclusion, we demonstrate that the sensitive detection of single molecule mutations in clinical specimens is feasible by SP-PCR. Our study confirms an earlier report that microsatellite mutations increase with age and is the first to provide evidence that these mutations may be associated with cancer status in individual subjects.

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Section: Discussionmentioning

confidence: 91%

Microsatellite mutations in buccal cells are associated with aging and head and neck carcinoma

Slebos

Vadivelu

et al. 2008

Br J Cancer

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“…P16 methylation is a frequent event in laryngeal carcinoma and was detected in more than 80% of the squamous cell cancer of the larynx [62]. Recently, it is demonstrated that methylation of p16 is an early event in squamous cell carcinoma at the laryngopharyngeal region, implying that methylated p16 may have a clinical value in screening patients with early laryngeal carcinoma [63]. Koscielny et al proposed that methylated p16 had prognostic value in a follow-up period of 3 years [64].…”

Section: Epigenetic Alterations In Human Malignanciesmentioning

confidence: 99%

Epigenetic Dysregulation in Laryngeal Squamous Cell Carcinoma

Wong

Gao

et al. 2012

Journal of Oncology

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Laryngeal carcinoma is a common head and neck cancer with poor prognosis. Patients with laryngeal carcinoma usually present late leading to the reduced treatment efficacy and high rate of recurrence. Despite the advance in the use of molecular markers for monitoring human cancers in the past decades, there are still no reliable markers for use to screen laryngeal carcinoma and follow the patients after treatment. Epigenetics emerged as an important field in understanding the biology of the human malignancies. Epigenetic alterations refer to the dysregulation of gene, which do not involve the alterations of the DNA sequence. Major epigenetic changes including methylation imbalance, histone modification, and small RNA dysregulation could play a role in the development of human malignancies. Global epigenetic change is now regarded as a molecular signature of cancer. The characteristics and behavior of a cancer could be predicted based on the specific epigenetic pattern. We here provide a review on the understanding of epigenetic dysregulation in laryngeal carcinoma. Further knowledge on the initiation and progression of laryngeal carcinoma at epigenetic level could promote the translation of the knowledge to clinical use.

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“…Improper methylation status of the following genes has been identified thus far in laryngeal cancer: Retinoic acid receptor β (RARβ), death-associated protein kinase (DAPK), cyclin-dependent kinase inhibitor 2A (CDKN2A), MGMT, RASSF1A, fragile histidine triad, chromodomain-helicase-DNA-binding protein 5, cellular retinol binding protein 1 and HIC1 (12)(13)(14)(15)(16)(17)(18)(19). The majority of the studies reported certain correlations between the clinical course of the disease and the molecular changes identified.…”

Section: Discussionmentioning

confidence: 99%

Expression of the tumor suppressor gene hypermethylated in cancer 1 in laryngeal carcinoma

et al. 2015

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Abstract. Hypermethylated in cancer 1 (HIC1) is a putative suppressor gene, cooperating with TP53 in the regulation of apoptosis. The promoter site of this gene contains CpG islands susceptible to methylation. Altered methylation leads to the silencing of HIC1. Persistent loss of HIC1 function reflects the attenuation of proapoptotic characteristics of TP53 and may constitute the background for carcinogenesis. Altered methylation profiles along with diminished expression of HIC1 were documented in a number of solid neoplasms. The aim of this study was to evaluate the expression of the HIC1 gene in laryngeal carcinoma. RNA was extracted from samples of laryngeal cancer and corresponding healthy tissues of 21 patients with advanced laryngeal cancer (T3-T4). The amount of RNA (cDNA) was evaluated using reverse transcription-quantitative polymerase chain reaction with GADPH as the reference gene. Data demonstrated that HIC1 expression was significantly reduced in laryngeal cancer tissues. The relative expression of HIC1 was found to be ~40% lower in tumor samples compared to that in healthy controls. The median tumor/normal tissue ratio for HIC1 was 0.615. These results suggest that low HIC1 expression may be associated with neoplastic transformation in the larynx.

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Molecular Detection of Early-Stage Laryngopharyngeal Squamous Cell Carcinomas

Cited by 13 publications

References 17 publications

Microsatellite mutations in buccal cells are associated with aging and head and neck carcinoma

Microsatellite mutations in buccal cells are associated with aging and head and neck carcinoma

Epigenetic Dysregulation in Laryngeal Squamous Cell Carcinoma

Expression of the tumor suppressor gene hypermethylated in cancer 1 in laryngeal carcinoma

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