Decreased expression of MLH1, MSH2, PMS1 and PMS2 in pigmented lesions indicates accumulation of failed DNA repair along with malignant transformation and tumour progression

Korabiowska, M; H, Dengler; Kellner, S; Stachura, Jerzy; Schauer, A.

doi:10.3892/or.4.3.653

Cited by 4 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While most reports have demonstrated the role of mismatch repair genes in hereditary nonpolyposis colon cancer, it has also been shown to play a crucial role in the progression of several sporadic tumours. [16][17][18] As mentioned in the introduction, the role of APC in tumour biology is still unclear, although there has been some speculation concerning the function of this gene. [8][9][10][11] The relation between the APC gene and proliferation has been investigated comprehensively.…”

Section: Discussionmentioning

confidence: 99%

Analysis of adenomatous polyposis coli gene expression, APC locus-microsatellite instability and APC promoter methylation in the progression of melanocytic tumours

et al. 2004

View full text Add to dashboard Cite

Adenomatous polyposis coli gene (APC) defects have been demonstrated for the first time in familial adenomatous polyposis. Recent reports indicate that the APC gene is an intermediary between cell adhesion molecules and the cytoskeleton and that it may function as a gatekeeper of colonic epithelial proliferation. The objective of this study was to analyse APC's presence in lentigos, primary melanomas and melanoma metastases. By immunohistochemistry, APC was demonstrated in all lentigos, in 75 out of 88 primary melanomas and in 16 out of 28 melanoma lymphatic metastases. The percentage of immunolabelled tumour cells (APC index) in lentigos ranged between 5 and 69%, in primary melanomas between 0 and 98% and in melanoma metastases between 0 and 52%. Statistically significant differences between lentigos and primary melanomas and between lentigos and metastases in APC expression were found. In a multivariate analysis, APC showed an independent prognostic impact. Analysis of microsatellite instability in the APC locus was performed on 29 melanomas. Microsatellite instability was found in 5/29 melanomas and loss of heterozygosity in 1/29 melanomas. Promoter methylation of APC was found in 6/10 APC-negative primary melanomas and in 9/10 APC-negative melanoma lymphatic metastases investigated. We conclude about important role of APC alterations for melanoma progression.

show abstract

Section: Discussionmentioning

confidence: 99%

Analysis of adenomatous polyposis coli gene expression, APC locus-microsatellite instability and APC promoter methylation in the progression of melanocytic tumours

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Reduced or defective expression of MSH2 has been associated with high genomic instability, poor melanoma prognosis, and metastasis [ 95 , 96 ]. Reduced expression or function of MSH2 is either a result of mutation-derived dysfunction of MSH2 [ 94 – 97 ] or miR-21-mediated downregulation of MSH2 mRNA [ 98 ] (Figure 1 ).…”

Section: Mir-21 Enhances Genetic Instability Of Melanoma Cellsmentioning

confidence: 99%

MiR-21: an environmental driver of malignant melanoma?

Melnik

2015

J Transl Med

110

View full text Add to dashboard Cite

Since the mid-1950’s, melanoma incidence has been rising steadily in industrialized Caucasian populations, thereby pointing to the pivotal involvement of environmental factors in melanomagenesis. Recent evidence underlines the crucial role of microRNA (miR) signaling in cancer initiation and progression. Increased miR-21 expression has been observed during the transition from a benign melanocytic lesion to malignant melanoma, exhibiting highest expression of miR-21. Notably, common BRAF and NRAS mutations in cutaneous melanoma are associated with increased miR-21 expression. MiR-21 is an oncomiR that affects critical target genes of malignant melanoma, resulting in sustained proliferation (PTEN, PI3K, Sprouty, PDCD4, FOXO1, TIPE2, p53, cyclin D1), evasion from apoptosis (FOXO1, FBXO11, APAF1, TIMP3, TIPE2), genetic instability (MSH2, FBXO11, hTERT), increased oxidative stress (FOXO1), angiogenesis (PTEN, HIF1α, TIMP3), invasion and metastasis (APAF1, PTEN, PDCD4, TIMP3). The purpose of this review is to provide translational evidence for major environmental and individual factors that increase the risk of melanoma, such as UV irradiation, chemical noxes, air pollution, smoking, chronic inflammation, Western nutrition, obesity, sedentary lifestyle and higher age, which are associated with increased miR-21 signaling. Exosomal miR-21 induced by extrinsic and intrinsic stimuli may be superimposed on mutation-induced miR-21 pathways of melanoma cells. Thus, oncogenic miR-21 signaling may be the converging point of intrinsic and extrinsic stimuli driving melanomagenesis. Future strategies of melanoma treatment and prevention should thus aim at reducing the burden of miR-21 signal transduction.

show abstract

“…Germline mutations in mismatch repair genes such as PMS1, PMS2, MSH2 , MSH3, MSH6 , MLH1, and MLH3 cause hereditary nonpolyposis colorectal cancer [19], and somatic mutations in mismatch repair genes are common in sporadic colorectal cancers [20]. Loss of PMS1 has been identified in dermal melanomas but not uveal melanoma [21-23]. Microsatellite instability and mutations in mismatch repair genes MSH2 and MLH3 are infrequently found in uveal melanomas [24-26].…”

Section: Discussionmentioning

confidence: 99%

GNAQ and PMS1 Mutations Associated with Uveal Melanoma, Ocular Surface Melanosis, and Nevus of Ota

et al. 2019

View full text Add to dashboard Cite

G protein mutations are common in uveal melanomas, and the vast majority target amino acid residue Q209 in either GNAQ or GNA11. The GNAQ R183Q mutation is found in a small fraction of uveal melanomas. We report a patient with an unusual presentation of uveal melanoma arising at an early age in the setting of congenital skin and ocular surface melanosis. A 34-year-old Hispanic female with congenital bilateral nevus of Ota and ocular surface melanosis presented with progressive loss of visual acuity and was found to have a juxtapapillary uveal melanoma. She was treated with brachytherapy, but the tumor relapsed. She underwent enucleation that revealed mixed spindle and epithelioid uveal melanoma cells with no extraocular or lymphovascular spread. Next-generation sequencing performed on DNA isolated from the enucleation specimen identified a GNAQ R183Q mutation and a PMS1 truncation mutation. Cytogenetic profiling revealed no monosomy 3. These findings raise the possibility that uveal melanomas bearing G protein R183 mutations may have distinct clinicopathologic profiles compared to those with Q209 mutations. Furthermore, this is the first reported case of a mutation in the mismatch repair gene PMS1 associated with uveal melanoma.

show abstract

Decreased expression of MLH1, MSH2, PMS1 and PMS2 in pigmented lesions indicates accumulation of failed DNA repair along with malignant transformation and tumour progression

Cited by 4 publications

References 0 publications

Analysis of adenomatous polyposis coli gene expression, APC locus-microsatellite instability and APC promoter methylation in the progression of melanocytic tumours

Analysis of adenomatous polyposis coli gene expression, APC locus-microsatellite instability and APC promoter methylation in the progression of melanocytic tumours

MiR-21: an environmental driver of malignant melanoma?

GNAQ and PMS1 Mutations Associated with Uveal Melanoma, Ocular Surface Melanosis, and Nevus of Ota

Contact Info

Product

Resources

About