Comprehensive mutational analysis of CDKN2A and CDK4 in Greek patients with cutaneous melanoma

Nikolaou, Vasiliki; Kang, Xiaojing; Stratigos, Alexander; Gogas, Helen; Latorre, M C; Gabree, Michele; Plaka, M.; Njauw, Ching‐Ni Jenny; Kypreou, Katerina P.; Mirmigi, I.; Stefanaki, Irene; Tsao, Hensin

doi:10.1111/j.1365-2133.2011.10551.x

Cited by 33 publications

(24 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…22 Similarly, in a study of Greek families, Nikolaou et al reported that 22% of familial melanoma cases and 57% of individuals with multiple primary melanomas carried a CDKN2A mutation. 23 When melanoma cases were ascertained independent of family history, there was a much lower rate of mutation. The frequency of CDKN2A mutations in patients with a single primary melanoma or multiple primary melanomas were 1.2% and 2.9%, respectively.…”

Section: 2b the Genetics Of Fammmmentioning

confidence: 99%

Hereditary melanoma: Update on syndromes and management

Soura

Eliades

Shannon

et al. 2016

Journal of the American Academy of Dermatology

175

View full text Add to dashboard Cite

Malignant melanoma is considered the most lethal skin cancer if not detected and treated at its early stages. About 10% of melanoma patients report a family history of melanoma; however, individuals with features of true hereditary melanoma (i.e. unilateral lineage, multi-generational, multiple primary lesions, and early onset of disease) are in fact quite rare. Although many new loci have been implicated in hereditary melanoma, CDKN2A mutations remain the most common. Familial melanoma in the presence of multiple atypical nevi should raise suspicion for a germline CDKN2A mutation. Such patients have a high risk of developing multiple primary melanomas and internal organ malignancies especially pancreatic cancer; thus, a multidisciplinary approach is necessary in many cases. The value of dermoscopy examination and total body photography performed at regular intervals has been suggested by a number of studies, and should therefore be considered for these patients and their first degree relatives. In addition, genetic counseling with the possibility of testing can be a valuable adjunct for familial melanoma patients. But, this must be performed with care and only by qualified individuals trained in cancer risk analysis.

show abstract

Section: 2b the Genetics Of Fammmmentioning

confidence: 99%

Hereditary melanoma: Update on syndromes and management

Soura

Eliades

Shannon

et al. 2016

Journal of the American Academy of Dermatology

175

View full text Add to dashboard Cite

show abstract

“…In addition to PTEN alterations, mutations of CDKN2A, as well as NRAS mutations have been frequently observed in melanoma [102,103]. CDKN2A is the most often mutated tumor suppressor gene in melanoma, with 60% homozygous deletions and additional 15-20% point mutations [104][105][106].…”

Section: Pten Mutations and Other Genesmentioning

confidence: 99%

Genetic alterations of PTEN in human melanoma

Aguissa-Touré

Li²

2011

Cell. Mol. Life Sci.

131

View full text Add to dashboard Cite

The PTEN gene is one of the most frequently inactivated tumor suppressor genes in sporadic cancers. Inactivating mutations and deletions of the PTEN gene are found in many types of cancers, including melanoma. However, the exact frequency of PTEN alteration in melanoma is unknown. In this study, we comprehensively reviewed 16 studies on PTEN genetic changes in melanoma cell lines and tumor biopsies. To date, 76 PTEN alterations have been reported in melanoma cell lines and 38 PTEN alterations in melanoma biopsies. The rate of PTEN alterations in melanoma cell lines, primary melanoma, and metastatic melanoma is 27.6, 7.3, and 15.2%, respectively. Three mutations were found in both melanoma cell lines and biopsies. These mutations are scattered throughout the gene, with the exception of exon 9. A mutational hot spot is found in exon 5, which encodes the phosphatase activity domain. Evidence is also presented to suggest that numerous homozygous deletions and missense variants exist in the PTEN transcript. Studying PTEN functions and implications of its mutations and other genes could provide insights into the precise nature of PTEN function in melanoma and additional targets for new therapeutic approaches.

show abstract

“…The prevalence of CDKN2A mutations is higher among the Greek population (which has a relatively low baseline risk of melanoma) compared to other reported cohorts, suggesting the strength of genetic factors in melanomagenesis (Nikolaou et al 2011 The cyclin-dependent kinase 4 (CDK4) gene locus encodes an enzyme that is inhibited by binding of p16 and is also found to be mutated among clusters of melanoma families (Zuo et al 1996), although CDK4 mutations are more rare than CDKN2A gene mutations. A study of 17 known families with CDK4 germline mutations showed that there are no phenotypically distinguishing features from CDKN2A families (Puntervoll et al 2013).…”

Section: Melanoma Phenotypes With Known Genetic Associations Loci Assmentioning

confidence: 87%

Melanoma: Clinical Features and Genomic Insights

Hawryluk

Tsao

2014

Cold Spring Harbor Perspectives in Medicine

Self Cite

View full text Add to dashboard Cite

Recent efforts in genomic research have enabled the characterization of molecular mechanisms underlying many types of cancers, ushering novel approaches for diagnosis and therapeutics. Melanoma is a molecularly heterogeneous disease, as many genetic alterations have been identified and the clinical features can vary. Although discoveries of frequent mutations including BRAF have already made clinically significant impact on patient care, there is a growing body of literature suggesting a role for additional mutations, driver and passenger types, in disease pathophysiology. Although some mutations have been strongly associated with clinical phenotypes of melanomas (such as physical distribution or morphologic subtype), the function or implications of many of the recently identified mutations remains less clear. The phenotypic and clinical impact of genomic mutations in melanoma remains a promising opportunity for progress in the care of melanoma patients. There have been many recent advances in our understanding of melanoma, from a greater appreciation of epidemiologic trends and risk factors to an increased understanding of the molecular genomics and biology of melanoma. Studies suggest that a number of molecularly distinct changes have a role in the pathophysiology of melanoma, and melanomas encompass a heterogeneous group when considering many known genomic alterations and diverse clinical phenotypes. To date, there are clinical subtypes or "phenotypes" of melanoma that are associated with specific genomic changes, in addition to many identified genomic mutations that lack a clear clinical correlation.Genomic studies are able to inform us about the disease phenotype, in addition to improving our understanding of disease pathogenesis. The various phenotypes of melanoma are characterized by clinical features, such as bodily distribution or risk factors. Cutaneous, uveal, acral, and mucosal melanomas (Fig. 1) have divergent clinical courses and are associated with distinct mutations, and risk factors such as skin phototype or UV exposure pattern are also associated with distinct alterations in genetic mutations. A melanoma phenotype can also be classified based on histopathologic morphology such as superficial spreading, nodular, desmoplastic, etc. In this review, we examine a number of Editors: Anthony E. Oro and Fiona M. Watt Additional Perspectives on The Skin and Its Diseases available at www.perspectivesinmedicine.org

show abstract

Comprehensive mutational analysis of CDKN2A and CDK4 in Greek patients with cutaneous melanoma

Cited by 33 publications

References 15 publications

Hereditary melanoma: Update on syndromes and management

Hereditary melanoma: Update on syndromes and management

Genetic alterations of PTEN in human melanoma

Melanoma: Clinical Features and Genomic Insights

Contact Info

Product

Resources

About