Increased C-MYC copy numbers on the background of CDKN2A loss is associated with improved survival in nodular melanoma

Koynova, Denitsa; Jordanova, Ekaterina S.; Kukutsch, Nicole A.; Velden, Pieter van der; Toncheva, Draga; Gruis, Nelleke A.

doi:10.1007/s00432-006-0150-4

Cited by 10 publications

(5 citation statements)

References 23 publications

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“…In our study, MYC copy number gain was distributed throughout all RCM CM types while CDKN2A homozygous deletion was identified in RCM CM types 3 and 4, conventionally associated with the nodular CM subtype, the most rapidly growing and aggressive variant of CM . This finding of combined MYC gain and CDKN2A deletion in RCM CM types 3 and 4 could indicate that the accumulation of consecutive genetic aberrations may lead to a more invasive phenotype, tumor progression and invasion . As previously suggested, our data might confirm that MYC and CDKN2A aberrations contribute to the development of the invasive potential of the primary tumor rather than to the metastatic process …”

Section: Discussionsupporting

confidence: 87%

“…Several studies have investigated the prognostic significance of MYC and CDKN2A aberrations in patients with CM . In the nodular subtype, Koynova et al observed that combined MYC gain and CDKN2A deletion were detected exclusively in tumors >1.1 mm in thickness. In our study, MYC copy number gain was distributed throughout all RCM CM types while CDKN2A homozygous deletion was identified in RCM CM types 3 and 4, conventionally associated with the nodular CM subtype, the most rapidly growing and aggressive variant of CM .…”

Section: Discussionmentioning

confidence: 99%

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Melanoma types by in vivo reflectance confocal microscopy correlated with protein and molecular genetic alterations: A pilot study

Beretti

Bertoni

Farnetani

et al. 2019

Experimental Dermatology

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Cutaneous melanoma (CM) is one of the most prevalent skin cancers, which lacks both a prognostic marker and a specific and lasting treatment, due to the complexity of the disease and heterogeneity of patients. Reflectance confocal microscopy (RCM) in vivo analysis is a versatile approach offering immediate morphological information, enabling the identification of four primary cutaneous RCM CM types. Whether RCM CM types are associated with a specific protein and molecular genetic profiles at the tissue level remains unclear. The current pilot study was designed to identify potential correlations between RCM CM types and specific biological characteristics, combining immunohistochemistry (IHC) and molecular analyses. Eighty primary CMs evaluated at patient bedside with RCM (type 1 [19, 24%], type 2 [12, 15%], type 3 [7, 9%] and type 4 [42, 52%]) were retrospectively evaluated by IHC stains (CD271, CD20, CD31, cyclin D1), fluorescence in situ hybridization FISH for MYC gain and CDKN2A loss and molecular analysis for somatic mutations (BRAF, NRAS and KIT). RCM CM types correlated with markers of stemness property, density of intra‐tumoral lymphocytic B infiltrate and cyclin D1 expression, while no significant association was found with blood vessel density nor molecular findings. RCM CM types show a different marker profile expression, suggestive of a progression and an increase in aggressiveness, according to RCM morphologies.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Melanoma types by in vivo reflectance confocal microscopy correlated with protein and molecular genetic alterations: A pilot study

Beretti

Bertoni

Farnetani

et al. 2019

Experimental Dermatology

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“…Several comparative genomic hybridization studies provide evidence for overrepresentation of the long arm of chromosome 20 in malignant melanoma. These studies also suggest that chromosome 20q contains genes that may contribute to melanoma pathogenesis [28,29]. However, the specific genes that are highly expressed due to DNA amplification of chromosome 20q are yet to be determined.…”

Section: Discussionmentioning

confidence: 99%

The Clinical Effect of the Inhibitor of Apopotosis Protein Livin in Melanoma

et al. 2012

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Objective: The inhibitor of apoptosis protein (IAP) livin is frequently overexpressed in melanoma. Livin binds caspases and thereby inhibits apoptosis. We found that caspases cleave livin to produce a truncated form with a paradoxical proapoptotic activity. Methods: We assessed the correlation of livin expression with survival among 114 melanoma patients treated with an autologous melanoma vaccine. In 52 patients, resection resulted in no evidence of disease (NED) and 62 remained with active disease (WAD). Protein levels were assessed using Western blot. Results: We found livin protein expression in 44/114 samples (38.4%). Median overall survival was 1.4 years in NED patients with high levels of livin protein, 8.4 years in those with low-intermediate levels and not reached in patients who did not express livin (p = 0.025). The corresponding overall survival was 2.3 years among WAD patients with high levels of livin protein, 11.3 years in those with low-intermediate levels and, paradoxically, only 4.0 years in patients who did not express livin (p = 0.012). Conclusion: Livin protein expression may play a role in the progression of melanoma and correlates with survival. A high level of the protein is associated with a poor prognosis. However, in WAD patients low to intermediate level of livin, rather than absence of the protein, is associated with a favorable prognosis. This is probably due to the paradoxical proapoptotic activity of this important regulator of apoptosis.

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“…Loss of 9p21.3, which includes CDKN2A and CDKN2B genes, is associated with poor prognosis [80]. Moreover, CDKN2A deletions combined with C-MYC increased copy number changes seem to be related to a low metastatic potential and better patient outcomes in primary nodular melanoma [81]. Although gene CDKN2A is predominantly deleted, rare amplification can occur [66].…”

Section: Familial Melanomamentioning

confidence: 99%

Copy number variations in malignant melanoma: genomic regions, biomarkers, and therapeutic targets

Lukáčová,

Pös,

Túryová

et al. 2024

neo

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Malignant melanoma is a skin tumor arising from melanocytes, occurring mostly in predisposed individuals. Melanomas are frequently present with copy number variations (CNVs), i.e., gains or losses of specific DNA regions that have provided immense potential for disease diagnosis and classification. The methodology of CNV detection has revolutionized in past decades, and current high throughput technologies enable us to analyze the entire spectrum of CNV alterations at the whole genome scale. Thus, identifying novel CNV biomarkers and evaluating their applicability in biomedicine are becoming increasingly important. The aim of this review was to summarize copy number changes occurring in malignant melanomas. We made an overview of specific genes and chromosomal locations affected in sporadic and familial melanoma and also of known germline alterations in melanoma-prone families. We summarized genomic regions aberrant in malignant melanoma and highlighted those frequently discussed in the literature, suggesting 7q, 11q, 12q, 9p, and 1q, but also others, as the most affected ones.

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Increased C-MYC copy numbers on the background of CDKN2A loss is associated with improved survival in nodular melanoma

Abstract: We conclude that the C-MYC increased copy number changes on the background of CDKN2A deletions seem to be related to a low metastatic potential and better patients' outcome in primary NMs.

Cited by 10 publications

References 23 publications

Melanoma types by in vivo reflectance confocal microscopy correlated with protein and molecular genetic alterations: A pilot study

Melanoma types by in vivo reflectance confocal microscopy correlated with protein and molecular genetic alterations: A pilot study

The Clinical Effect of the Inhibitor of Apopotosis Protein Livin in Melanoma

Copy number variations in malignant melanoma: genomic regions, biomarkers, and therapeutic targets

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