Consistent DNA Hypermethylation Patterns in Laryngeal Papillomas

Stephen, Josena K.; Chen, Kang Mei; Shah, Veena; Schweitzer, Vanessa G.; Gardner, Glendon M.; Benninger, Michael S.; Worsham, Maria J.

doi:10.5005/jp-journals-10001-1013

Cited by 17 publications

(17 citation statements)

References 41 publications

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“…The lack of methylation in HPV6 is in agreement with a recent study demonstrating the absence of methylation in the URR of HPV11 from a single patient with laryngeal papillomas (8). Nevertheless, the lack of methylation within our series of HPV6 URRs was unexpected, since a high frequency of hypermethylation has been observed in host tumor suppressor genes in laryngeal papillomas (25). However, HPV6 has also been detected in nondiseased respiratory sites (17,22), and it is tempting to speculate that expression of HPV6 is repressed by methylation in such tissues.…”

supporting

confidence: 78%

Lack of Methylation in the Upstream Region of Human Papillomavirus Type 6 from Aerodigestive Tract Papillomas

Ure

Forslund

2012

J Virol

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Methylation of the high-risk human papillomavirus type 16 (HPV16) upstream regulatory region (URR) has been described, but whether methylation is present among low-risk HPVs is unknown. The methylation status of the HPV6 URR was analyzed in papillomas from the upper aerodigestive tract of six adult patients. All CpGs in the URR were unmethylated, from both basal/ intermediate and superficial cells, suggesting that methylation is not involved in the regulation of transcription from the HPV6 URR, regardless of epithelial differentiation.

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supporting

confidence: 78%

Lack of Methylation in the Upstream Region of Human Papillomavirus Type 6 from Aerodigestive Tract Papillomas

Ure

Forslund

2012

J Virol

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“…It is extremely easy to perform and is an inexpensive one-tube assay compared to array based technologies. MS-MLPA has been validated in other studies by our group [44,45] with a high degree of sensitivity and specificity as well as by MRC Holland [46], the makers of MS-MLPA. MRC Holland demonstrated the sensitivity of MS-MLPA by analyzing human sample DNA methylated in vitro which resulted in amplification products for all probes.…”

Section: Resultsmentioning

confidence: 92%

DNA Methylation in Thyroid Tumorigenesis

Stephen

Chitale

Narra³

et al. 2011

Cancers

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Thyroid cancer is the most common endocrine cancer with 1,690 deaths each year. There are four main types of which the papillary and follicular types together account for >90% followed by medullary cancers with 3% to 5% and anaplastic carcinomas making up <3%. Epigenetic events of DNA hypermethylation are emerging as promising molecular targets for cancer detection. Our immediate and long term goal is to identify DNA methylation markers for early detection of thyroid cancer. This pilot study comprised of 21 patients to include 11 papillary thyroid cancers (PTC), 2 follicular thyroid cancers (FTC), 5 normal thyroid cases, and 3 hyperthyroid cases. Aberrant promoter methylation was examined in 24 tumor suppressor genes using the methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) assay and in the NIS gene using methylation-specific PCR (MSP). The frequently methylated genes were CASP8 (17/21), RASSF1 (16/21) and NIS (9/21). In the normal samples, CASP8, RASSF1 and NIS were methylated in 5/5, 4/5 and 1/5 respectively. In the hyperthyroid samples, CASP8, RASSF1 and NIS were methylated in 3/3, 2/3 and 1/3 respectively. In the thyroid cancers, CASP8, RASSF1, and NIS were methylated in 9/13, 10/13, and 7/13 respectively. CASP8, RASSF1 and NIS were also methylated in concurrently present normal thyroid tissue in 3/11, 4/11 and 3/11 matched thyroid cancer cases (matched for presence of both normal thyroid tissue and thyroid cancer), respectively. Our data suggests that aberrant methylation of CASP8, RASSF1, and NIS maybe an early change in thyroid tumorigenesis regardless of cell type.

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“…HPV status for the primary and late stomal tumor biopsies was identified and confirmed by PCR for HPV-11 and HPV-16 sequences using multiple HPV type specific primers especially designed to amplify less than 300 base pair DNA fragment lengths (34) (Figure 2). …”

Section: Methodsmentioning

confidence: 99%

Molecular characterization of late stomal recurrence following total laryngectomy

et al. 2011

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The goal was to determine recurrent or second primary status for late stomal malignancies, 16 and 17 years post-total laryngectomy in two laryngeal squamous cell carcinoma (LSCC) patients, based on DNA methylation signatures and HPV typing. Adopting a literature review based definition of late stomal recurrences as new primaries at the site of the stoma or neopharynx occurring more than 5 years after total laryngectomy, we employed a multi-gene candidate approach to examine promoter methylation in 24 tumor suppressor genes and PCR-based assays for HPV status offered additional insights into whether the late stomal tumors post total laryngectomy were related or not. The primary tumor for Patient 1 was negative for HPV but had aberrant hypermethylation of APC, MLH1, and BRCA1. The stomal biopsy 17-years later showed presence of HPV-16 without any methylated genes. In Patient 2, HPV-11 and promoter methylation of APC identified in the primary tumor was also observed in the stomal malignancy 16 years post total laryngectomy. Additional information provided by molecular typing for HPV and methylation markers underscored Patient 1’s and 2’s late stomal presentation as most likely a second primary and recurrence, respectively. DNA methylation markers are particularly advantageous because DNA methylation is an early event in tumorigenesis, and the epigenetic modification, 5-methylcytosine, is a stable marker. Molecular marks to discern genetic heterogeneity or relatedness of stomal malignancies several years post-total laryngectomy can provide clues to their status as either second primaries or likely recurrences. Our results support the hypothesis that a subset of stomal recurrences after total laryngectomy represents second primary tumors.

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Consistent DNA Hypermethylation Patterns in Laryngeal Papillomas

Cited by 17 publications

References 41 publications

Lack of Methylation in the Upstream Region of Human Papillomavirus Type 6 from Aerodigestive Tract Papillomas

Lack of Methylation in the Upstream Region of Human Papillomavirus Type 6 from Aerodigestive Tract Papillomas

DNA Methylation in Thyroid Tumorigenesis

Molecular characterization of late stomal recurrence following total laryngectomy

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