Inactivation of human mutL homolog 1 and mutS homolog 2 genes in head and neck squamous cell carcinoma tumors and leukoplakia samples by promoter hypermethylation and its relation with microsatellite instability phenotype

Sengupta, Shiladitya; Chakrabarti, Swarup K.; Roy, Anup; Panda, Chinmay Kumar; Roychoudhury, Susanta

doi:10.1002/cncr.22430

Cited by 44 publications

(43 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reduced expression of p53 might be due to deletion/mutation as seen in HNSCC samples (Mitra et al, 2007). Frequent genomic instability in HNSCC samples of Indian patient has also been reported (Sengupta et al, 2007). It seems that p53 inactivation in mild dysplastic lesions might provide some selective pressure for outgrowth of cells having genomic instability along with aberrations in cell cycle and other signaling pathways as mentioned above.…”

Section: Discussionmentioning

confidence: 90%

Reduced Expression of Limd1 in Ulcerative Oral Epithelium Associated with Tobacco and Areca Nut

Maiti

Ghosh²,

Chatterjee³

et al. 2012

Asian Pacific Journal of Cancer Prevention

Self Cite

View full text Add to dashboard Cite

Purpose: The aim of this study was to cast light on initiating molecular events associated with the development of premalignant oral lesions induced by tobacco and/or areca nut. Method: Immunohistochemical analyses of cell cycle regulatory proteins (LIMD1, RBSP3, p16, RB, phosphorylated RB, p53), EGFR and SH3GL2 (EGFR associated protein) were performed with inflammatory/ ulcerative epithelium and adjacent hyperplastic/mild dysplastic lesions. Results: No change in expression of the proteins was seen in inflammatory epithelium. Reduced nuclear expression of LIMD1 was evident in ulcerative epithelium. In hyperplastic lesions, reduced expression of RBSP3, p16, SH3GL2 and overexpression of p-RB and EGFR were apparent. Reduced nuclear expression of p53 was observed in mild dysplastic lesions. Conclusion: Our data suggest that inactivation of LIMD1 in ulcerative epithelium might predispose the tissues to alterations of other cell cycle regulatory and EGFR signaling proteins needed for the development of premalignant oral lesions.

show abstract

Section: Discussionmentioning

confidence: 90%

Reduced Expression of Limd1 in Ulcerative Oral Epithelium Associated with Tobacco and Areca Nut

Maiti

Ghosh²,

Chatterjee³

et al. 2012

Asian Pacific Journal of Cancer Prevention

Self Cite

View full text Add to dashboard Cite

show abstract

“…Similar trend has also been reported by others where high frequency of methylation in several genes have been found in histologically normal tissues adjacent to tumor and premalignant lesions, suggesting that methylation is an early event. 39,40 Interrelation between deletion and methylation status of the candidate genes…”

Section: Promoter Methylation Status Of the Candidate Tsgsmentioning

confidence: 99%

Alterations of 3p21.31 tumor suppressor genes in head and neck squamous cell carcinoma: Correlation with progression and prognosis

Ghosh

Maiti

et al. 2008

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

The aim of our study was to analyze the alterations of some candidate tumor suppressor genes (TSGs) viz. LIMD1, LTF, CDC25A, SCOTIN, RASSF1A and CACNA2D2 located in the chromosomal region 3p21.31 associated with the development of early dysplastic lesions of head and neck. In analysis of 72 dysplastic lesions and 116 squamous cell carcinoma of head and neck, both deletion and promoter methylation have been seen in these genes except for CDC25A and SCOTIN where no methylation has been detected. The alteration of LIMD1 was highest (50%) in the mild dysplastic lesions and did not change significantly during progression of tumor indicating its association with this stage of the disease. It was evident that alterations of LTF, CDC25A and CACNA2D2 were associated with development of moderate dysplastic lesions, while alterations in RASSF1A and CACNA2D2 were needed for progression. Novel somatic mutations were seen in exon 1 of LIMD1 (7%), intron 3/exon4 splice junction of LTF (2%) and exon 7 of cdc25A (10%). Quantitative RT-PCR analysis revealed mean reduced expression of the genes in the following order: LTF (67.6 6 16.8) > LIMD1 (53.2 6 20.1) > CACNA2D2 (23.7 6 7.1) > RASSF1A (15.1 6 5.6) > CDC25A (5.3 6 2.3) > SCOTIN (0.58 6 0.54). Immunohistochemical analysis of CDC25A showed its localization both in cytoplasm and nucleus in primary lesions and oral cancer cell lines. In absence of HPV infection, LTF and RASSF1A alterations jointly have adverse impact on survival of tobacco addicted patients. Thus, our data suggested that multiple candidate TSGs in the chromosomal 3p21.31 region were differentially associated with the early dysplastic lesions of head and neck. ' 2008 Wiley-Liss, Inc.Key words: dysplastic lesions; expression; head and neck squamous cell carcinoma; mutation; 3p21.31; survival study; tumor suppressor genes; methylation Head and neck squamous cell carcinoma of (HNSCC) is the sixth most common cancer worldwide and it accounts for 30-40% of all cancer types in Indian subcontinent.1 HNSCC is a heterogeneous epithelial malignant disease arising from mucosa of the upper aerodigestive tract (oral cavity, larynx, oropharynx and hypopharynx) with complex molecular abnormalities. Although the major and common environmental carcinogenic risk factors of tobacco, alcohol, betel quid and HPV infection have long been recognized, details of the genetic and epigenetic events leading to the development and spread of HNSCC remain largely unknown. Array-based gene expression profiling focused the transition of normal mucosa to premalignant lesion as the most important event with majority of transcriptional alterations rather than transition from premalignant lesion to invasive carcinoma during the progression of HNSCC.2 In microcell hybrid system, it has been shown that the introduction of chromosome 3 can suppress the tumorigenicity of oral cancer cell lines, suggesting the presence of at least 1 tumor suppressor gene (TSG) in this chromosome associated with the development of HNSCC.3 According to a recent tumor progr...

show abstract

“…For example, frequency of tandem duplications was correlated with specific subtypes of breast cancer, suggesting that disruption of crucial DNA maintenance pathways may underlie distinct mechanisms of transformation in different subtypes (Stephens et al 2009;Swanton et al 2011). Sequence-level alterations may also be driven by hypomethylation of normally heavily methylated repetitive DNA (Rizwana and Hahn 1999;Eden et al 2003;Daskalos et al 2009;Igarashi et al 2010;De and Michor 2011) or by aberrant promoter hypermethylation (silencing) of DNA repair genes (MLH1, CDKN2A)-as has been observed in several cancer types (Kane et al 1997;Sengupta et al 2007; Cancer Genome Atlas Research Network 2008; Vasavi et al 2010;Shima et al 2011;Tawfik et al 2011). In tumors with a high genomic alteration load, DNA alterations may be a consequence of disruption to genes maintaining genomic integrity.…”

Section: Deciphering Biologically Relevant Dna Mutationsmentioning

confidence: 94%

Translating cancer ‘omics’ to improved outcomes: Figure 1.

Vucic¹,

Thu²,

Robison³

et al. 2012

Genome Res.

107

View full text Add to dashboard Cite

The genomics era has yielded great advances in the understanding of cancer biology. At the same time, the immense complexity of the cancer genome has been revealed, as well as a striking heterogeneity at the whole-genome (or omics) level that exists between even histologically similar tumors. The vast accrual and public availability of multi-omics databases with associated clinical annotation including tumor histology, patient response, and outcome are a rich resource that has the potential to lead to rapid translation of high-throughput omics to improved overall survival. We focus on the unique advantages of a multidimensional approach to genomic analysis in this new high-throughput omics age and discuss the implications of the changing cancer demographic to translational omics research.

show abstract

Inactivation of human mutL homolog 1 and mutS homolog 2 genes in head and neck squamous cell carcinoma tumors and leukoplakia samples by promoter hypermethylation and its relation with microsatellite instability phenotype

Cited by 44 publications

References 91 publications

Reduced Expression of Limd1 in Ulcerative Oral Epithelium Associated with Tobacco and Areca Nut

Reduced Expression of Limd1 in Ulcerative Oral Epithelium Associated with Tobacco and Areca Nut

Alterations of 3p21.31 tumor suppressor genes in head and neck squamous cell carcinoma: Correlation with progression and prognosis

Translating cancer ‘omics’ to improved outcomes: Figure 1.

Contact Info

Product

Resources

About