Main roads to melanoma

Palmieri, Giuseppe; Capone, Mariaelena; Ascierto, Maria Libera; Gentilcore, Giusy; Stroncek, David F.; Casula, Milena; Sini, Maria Cristina; Palla, Marco; Mozzillo, Nicola; Ascierto, Paolo A.

doi:10.1186/1479-5876-7-86

Cited by 162 publications

(198 citation statements)

References 201 publications

(187 reference statements)

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“…To assess changes in gene expression associated with anchorage-independent growth, we isolated RNA from the melanocyte colonies that grew in soft agar and examined a panel of melanoma and cancer-specific markers by TaqMan reverse transcriptase PCR (Figure 10). Consistent with expectation (Hoek et al, 2004;Kuphal et al, 2006;Klein et al, 2007;Palmieri et al, 2009;Bandarchi et al, 2010), miR-506-514 overexpression and growth in soft agar was associated with substantial downregulation of E-cadherin, P-cadherin, p16/CDKN2A, DKK3, RAB33A, TYRP1 and BAD, as well as greatly increased expression of Ki67, MIA, DCT and the stem cell markers PROM1/ CD133 and Nestin. Other genes showed no changes in expression due to altered miR-506-514 levels.…”

Section: Resultssupporting

confidence: 74%

A novel oncogenic role for the miRNA-506-514 cluster in initiating melanocyte transformation and promoting melanoma growth

et al. 2011

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Malignant melanoma is the most aggressive form of skin cancer and its incidence has doubled in the last two decades. It represents only 4% of skin cancer cases per year, but causes as many as 74% of skin cancer deaths. Early detection of malignant melanoma is associated with survival rates of up to 90%, but later detection (stage III to stage IV) is associated with survival rates of only 10%. Dysregulation of microRNA (miRNA) expression has been linked to tumor development and progression by functioning either as a tumor suppressor, an oncogene or a metastasis regulator in multiple cancer types. To understand the role of miRNA in the pathogenesis of malignant melanoma and identify biomarkers of metastasis, miRNA expression profiles in skin punches from 33 metastatic melanoma patients and 14 normal healthy donors were compared. We identified a cluster of 14 miRNAs on the X chromosome, termed the miR-506-514 cluster, which was consistently overexpressed in nearly all melanomas tested (30-60 fold, Po0.001), regardless of mutations in N-ras or B-raf. Inhibition of the expression of this cluster as a whole, or one of its sub-clusters (Sub-cluster A) consisting of six mature miRNAs, led to significant inhibition of cell growth, induction of apoptosis, decreased invasiveness and decreased colony formation in soft agar across multiple melanoma cell lines. Sub-cluster A of the miR-506-514 cluster was critical for maintaining the cancer phenotype, but the overexpression of the full cluster was necessary for melanocyte transformation. Our results provide new insights into the functional role of this miRNA cluster in melanoma, and suggest new approaches to treat or diagnose this disease.

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Section: Resultssupporting

confidence: 74%

A novel oncogenic role for the miRNA-506-514 cluster in initiating melanocyte transformation and promoting melanoma growth

et al. 2011

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“…Leginkább olyan betegeknél jelentkezik, akiknek bőre intermittáló UV-sugárzásnak volt kitéve [19]. Ez a mutáció nemcsak a melanomák esetén detektálható, hanem előfordul papillaris pajzsmirigy-, ovárium-és colorectalis carcinomában is [20]. A mutációk 80%-ában a 15. exonon található 600-as kodont érintő báziscseréről van szó: az 1799-es pozícióban levő timin helyére egy adenin nukleotid kerül, amelyet T1799A-val jelölnek.…”

Section: Braf-mutáns Melanomaunclassified

Genetic diversity and immunological characteristics of malignant melanoma: the therapeutic spectrum

Doma

Gulya

2015

Orvosi Hetilap

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A malignus melanoma pigmentsejtekből kiinduló, későn felfedezve igen agresszív, folyamatosan növekvő incidenciá-jú, bármely korosztályt érintő daganatos megbetegedés. Leggyakoribb formája meglévő hajlamosító tényezők (bőr-, szem-, hajszín, anyajegyek, pozitív családi anamnézis) talaján hozzáadódó környezeti faktorok (napégés) hatására a kültakarón, vagyis minden orvos számára könnyen vizsgálható helyen alakul ki. Sikeres kezelésének alapja továbbra is a korai diagnózis és műtéti eltávolítás. Áttétek jelentkezésekor a klasszikus, bár melanoma esetén csekély sikerrel kecsegtető kemo-és sugárterápia mellett, illetve helyett ma már új, molekuláris genetikai kutatásokon alapuló célzott terápiás szerek, valamint a gátolt tumorellenes immunválaszt a fék alól felszabadító immunterápiás gyógyszerek is rendelkezésre állnak. Az összefoglaló közleményben a szerzők régi és új ismereteket igyekeznek rendszerezni és terjeszteni, bármely, a téma iránt mélyebben érdeklődő gyógyító szakma képviselőjének átnyújtani. Orv. Hetil., 2015, 156(15), 583-591. Kulcsszavak: malignus melanoma, célzott terápia, jelátviteli útvonal, immunterápiaGenetic diversity and immunological characteristics of malignant melanoma: the therapeutic spectrum Malignant melanoma, originating from pigment cells, is a highly aggressive tumour affecting patients of any age group. Its incidence is rapidly growing. The most common form can be easily diagnosed by any physician. There are some well-known genetic (skin-, eye-, hair colour, naevi, melanoma in the personal/family history) and environmental (ultraviolet radiation) predisposing factors. Treatment is based on early diagnosis and excision. When metastasis occurs, the traditional chemo-and radiotherapy gives a low response rate. Recently some newly approved targeted therapies and immunomodulant drugs have become available. This review focuses on the classifi cation and novel therapeutic approaches of malignant melanoma to provide guidance to clinicians.

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“…Melanoma is the most aggressive type of cutaneous malignancy and is responsible for 80% of mortalities from skin cancer, despite accounting for only 4% of all cases of dermatological cancer (1). Typically, melanoma is histologically diagnosed with the aid of specific protein markers, including S100, melanoma-associated antigen recognized by T cells-1 (MART-1) and human melanoma black-45 (HMB-45).…”

Section: Introductionmentioning

confidence: 99%

Atypical amplification of chromosome region 22q12 in melanoma: A case report

et al. 2015

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Abstract. Morphological, ultrastructural and immunohistochemical characteristics of clear cell sarcoma (CCS) of the soft tissue frequently overlap with those of malignant melanoma. Thus, the differential diagnosis between the two lesions represents an important diagnostic dilemma. However, a number of genetic factors can be used to differentiate the two tumors; in particular, the t(12;22)(q13;q12) chromosomal translocation is typical of CCS, resulting in fusion of the EWSR1 gene on chromosome 22q12 and the ATF1 gene on chromosome 12q13. The detection of this molecular alteration has proved useful in the differential diagnosis of the two lesions. The present study reports the case of a 71-year-old male patient with a suspicious lymph node mass. Immunohistochemical analysis of the lesion indicated a diagnosis of metastatic melanoma, however, cytogenetic analysis using fluorescence in situ hybridization was additionally performed to investigate the chromosomal rearrangements of the 22q12 region and completely exclude the possibility of CCS. The current case did not demonstrate the presence of the translocation, supporting the diagnosis of melanoma. However, a clear orange amplification signal was observed relative to an ~500-kb region adjacent to the EWSR1 gene in the centromeric direction of chromosome 22q12. To the best of our knowledge, this is the first description of a 22q12 chromosomal alteration in melanoma. Furthermore, despite the presence of numerous genes in this region, their amplification has not previously been associated with the pathogenesis of melanoma. IntroductionMelanoma is the most aggressive type of cutaneous malignancy and is responsible for 80% of mortalities from skin cancer, despite accounting for only 4% of all cases of dermatological cancer (1). Typically, melanoma is histologically diagnosed with the aid of specific protein markers, including S100, melanoma-associated antigen recognized by T cells-1 (MART-1) and human melanoma black-45 (HMB-45). Additionally, the diagnosis of malignant melanoma (MM) is commonly supported by the detection of BRAF mutations (2).By contrast, clear cell sarcoma (CCS), previously known as melanoma of the soft parts, is an uncommon type of malignant tumor. CCS typically presents as a deep soft-tissue mass, and microscopically and immunohistochemically demonstrates evidence of melanocytic differentiation (3).While the majority of CCS occurs in the deep soft tissue, superficial variants have recently been reported in the dermis and/or superficial subcutis. Such CCS may be confused with primary melanoma or MM, as CCS and MM can stain positively for S100 and HMB-45 (4,5). Determination of the differential diagnosis of these tumors is facilitated by the result of a previously conducted cytogenetic study that identified the presence of a characteristic t(12;22) chromosomal translocation involving the EWSR1 gene in 70-90% of CCS cases (6).The current study reports the case of a 71-year-old male who presented with a suspicious lymph node mass. The final diagnosis of ...

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Main roads to melanoma

Cited by 162 publications

References 201 publications

A novel oncogenic role for the miRNA-506-514 cluster in initiating melanocyte transformation and promoting melanoma growth

A novel oncogenic role for the miRNA-506-514 cluster in initiating melanocyte transformation and promoting melanoma growth

Genetic diversity and immunological characteristics of malignant melanoma: the therapeutic spectrum

Atypical amplification of chromosome region 22q12 in melanoma: A case report

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