Abstract:
:A proportion of patients diagnosed with melanoma has a positive family history. Despite increasing knowledge on the genes responsible for familial clustering, the genetic basis in the majority of the families with an inherited predisposition to melanoma remains to be clarified. To identify novel melanoma-susceptibility genes, we applied whole-exome sequencing on DNA from two members of a family with four melanoma cases, not explained by established high penetrance melanoma-susceptibility genes. Whole-exome sequencing identified 10 rare, co-segregating, predicted deleterious missense gene variants. Subsequent co-segregation analysis revealed that only variants in the DOT1L (R409H) and the SLCO4C1 (P597A) genes were present in the other two affected members of this family. DOT1L is a methyltransferase that methylates histone H3 lysine 79 (H3K79). It is involved in maintenance of genomic stability, since mutations in the DOT1L gene have been previously reported to compromise the removal of ultraviolet photoproducts in ultraviolet-irradiated melanocytes, thereby enhancing malignant transformation. We hypothesized that the presence of DOT1L R409H variant might be associated with an increased risk of melanoma, since we found co-segregation of the DOT1L mutation in all four melanoma-affected family members. However, this missense variant did neither lead to detectable loss-of-heterozygosity nor reduction of histone methyltransferase activity in melanoma samples from mutation carriers nor altered ultraviolet-survival of mouse embryonic stem cells containing an engineered homozygous DOT1L R409H mutation. Although functional analysis of this rare co-segregating variant did not reveal compromised histone methyltransferase activity and ultraviolet exposure sensitivity, the role of DOT1L as melanoma susceptibility gene deserves further study.
journal_name
Melanoma Resjournal_title
Melanoma researchauthors
Salgado C,Kwesi-Maliepaard EM,Jochemsen AG,Visser M,Harland M,van Leeuwen F,van Doorn R,Gruis Ndoi
10.1097/CMR.0000000000000640subject
Has Abstractpub_date
2019-12-01 00:00:00pages
582-589issue
6eissn
0960-8931issn
1473-5636journal_volume
29pub_type
杂志文章abstract::Reversible oxidation sensitivity of N-Oct-3 DNA binding activity was seen when melanoma extracts and recombinant Brn-2 protein were treated with a variety of metals, hydrogen peroxide and the cysteine disulphide bond forming agent diamide. Western blot analysis of diamide-oxidized N-Oct-3 protein indicated that this w...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199802000-00002
更新日期:1998-02-01 00:00:00
abstract::We studied the response of mouse B16F10 and SK-MEL-28 and SK-MEL-1 human melanoma cell lines to treatment with 4-hydroxyanisole (4-HA), and attempted to relate the response to the dopa oxidase levels and the morphological characteristics of each cell line. Clear dose-response curves were observed after 24 h of treatme...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199710000-00003
更新日期:1997-10-01 00:00:00
abstract::Dissemination of uveal melanomas is almost exclusively haematogenous, making angiogenesis of the tumour a prerequisite for the formation of metastases. Uveal melanomas must employ strategies to evade the immune system in order to escape immune surveillance. We therefore determined the expression of the following angio...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199910000-00003
更新日期:1999-10-01 00:00:00
abstract::Interleukin-24 (IL-24)/melanoma differentiation-associated gene-7 (mda-7) is a unique cytokine-tumor suppressor that displays ubiquitous antitumor properties and tumor-specific killing activity. Oncostatin M (OSM) is the most active IL-6-type cytokine and inhibits the proliferation of various solid tumor cell lines. M...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000038
更新日期:2014-02-01 00:00:00
abstract::Immunotherapy with anti-programmed cell death-1 (PD-1) agents is an effective treatment for metastatic melanoma. Octogenarians and nonagenarians represent a significant cohort of melanoma patients. This multicenter retrospective analysis enrolled 499 patients treated with nivolumab or pembrolizumab. Seventy-three pati...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000705
更新日期:2021-02-01 00:00:00
abstract::Recently, TROG 02.01 results showed that in stage III melanoma patients with nodal metastasis, adjuvant radiation to lymph node basin after nodal dissection improves lymph node field relapse without an overall survival (OS) benefit. However, this trial was neither designed nor powered to detect an OS difference. In th...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000292
更新日期:2016-12-01 00:00:00
abstract::Proteomics provides a powerful approach for screening alterations in protein expression and post-translational modification associated with particular human diseases. In this study, the analysis of protein expression was focused on malignant melanoma in order to determine the candidate genes involved in tumour progres...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200508000-00002
更新日期:2005-08-01 00:00:00
abstract::Melan-A is widely used in the diagnostics of human melanoma. The immunogenicity of this glycoprotein makes it a potential target in immunotherapy and several authors have suggested its potential as a prognostic factor. Up to now there has been no clear direct evidence of changes of Melan-A expression during the progre...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e328303beac
更新日期:2008-08-01 00:00:00
abstract::The concept of 'vasculogenic mimicry' (VM) was introduced to describe the unique ability of highly invasive tumor cells to form capillary-like structures (CLS) and matrix-rich patterned network in three-dimensional culture that mimic embryonic vasculogenic network. Recently, we have shown that CLS formation requires a...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3282f1d2ec
更新日期:2007-12-01 00:00:00
abstract::Melanoma is the deadliest form of skin cancer. Ipilimumab, a novel immunotherapy, is the first treatment shown to improve survival in patients with metastatic melanoma in large randomized controlled studies. The most concerning side effects reported in clinical studies of ipilimumab fall into the category of immune-re...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e32835c7e68
更新日期:2013-02-01 00:00:00
abstract::Ultraviolet-B (UV-B) triggers a cascade of events involving cell cycle control genes leading ultimately to DNA repair or apoptosis. The hypothesis examined here is that the genetic abnormality predisposing to melanoma affects the ability of the cell to respond appropriately to UV-B, so favouring mutagenesis. Epstein-B...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200102000-00001
更新日期:2001-02-01 00:00:00
abstract::Pregnancy-associated melanoma is defined as melanoma diagnosed during pregnancy or within 1 year of delivery. The association of pregnancy with melanoma is well known, but its underlying molecular mechanisms of association are poorly understood. The aim was to assess the expression of apoptosis-related genes in melano...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000452
更新日期:2018-08-01 00:00:00
abstract::Cellular senescence is a major barricade on the path of cancer development, yet proteins secreted from senescent cells exert complex and often discordant effects on subsequent cancer evolution. Somatic genome alternations driving the formation of nevi and melanoma are efficient inducers of cellular senescence. Melanoc...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000671
更新日期:2020-08-01 00:00:00
abstract::Genes in the S100 family are abnormally expressed in a variety of tumor cells and are associated with clinical pathology, but their prognostic value in melanoma patients has not yet been fully elucidated. In this study, we extracted and profiled S100 family mRNA expression data and corresponding clinical data from the...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000512
更新日期:2019-02-01 00:00:00
abstract::Treatment strategies for metastatic melanoma have changed markedly in recent times due to the advent of targeted systemic therapies. In addition to these developments, surgery remains a useful adjunct that can confer survival benefits in selected patients. In this review, we examine the current literature to highlight...
journal_title:Melanoma research
pub_type: 杂志文章,评审
doi:10.1097/CMR.0000000000000128
更新日期:2015-02-01 00:00:00
abstract::CD8 T-cell infiltration of metastatic melanoma may be a useful biomarker for prediction of prognosis and response to therapy. The heterogeneous distribution of CD8 T cells within a single tumor, and across different tumors within a single patient, may complicate quantification of infiltration. However, the impact of h...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000330
更新日期:2017-06-01 00:00:00
abstract::This study examines whether 6-thioguanine resistant T cells (mutant) from metastatic melanoma patients are enriched for melanoma-associated T cells compared to T cells obtained analogously without thioguanine selection (wild-type). Melanoma-associated antigen pentamer staining was performed on 5 tumour and 9 periphera...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000625
更新日期:2020-02-01 00:00:00
abstract::The management of metastatic melanoma is a difficult matter. Nevertheless, the advent of target therapy has significantly improved patient outcome, provided that tumor molecular characteristics become available: the detection of drug-resistant clones can contribute to understanding the reasons for resistance onset, in...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0000000000000510
更新日期:2019-02-01 00:00:00
abstract::In this study we evaluated the overexpression status of HER-2 and its prognostic significance on survival in patients with thick cutaneous malignant melanoma. The immuno-alkaline phosphatase antigen detection technique was applied to archival diagnostic material from 51 patients with primary lesions measuring >or= 10 ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200204000-00006
更新日期:2002-04-01 00:00:00
abstract::Melanoma is the most lethal skin tumor in large part because of a propensity for early metastasis. Good models of this most clinically relevant feature of melanoma are lacking. Here, we report the development of an in-vivo model of metastasis that relies on orthotopic injection of green fluorescent protein-tagged line...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e328336ee17
更新日期:2010-10-01 00:00:00
abstract::We assessed the risk of cutaneous malignant melanoma associated with the presence of ovulatory abnormalities and with the use of ovulation-inducing agents (such as clomiphene citrate) in a cohort of 3,837 women evaluated at infertility clinics in Seattle, WA, between 1974 and 1985. Computer linkage with a population-b...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199504000-00009
更新日期:1995-04-01 00:00:00
abstract::MicroRNAs (miRNAs) are small noncoding RNA molecules involved in gene regulation. Aberrant expression of miRNA has been associated with the development or progression of several diseases, including cancer. In a previous study, we found that the expression of miRNA-125b (miR-125b) was two-fold lower in malignant melano...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e328345333b
更新日期:2011-06-01 00:00:00
abstract::Resistance to various antineoplastic agents is common in the clinical management of malignant melanoma. The biological mechanisms conferring these different drug-resistant phenotypes are still unclear. To identify potential factors mediating drug resistance to melanoma cells, the mRNA expression profiles of the parent...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/01.cmr.0000215037.23188.58
更新日期:2006-04-01 00:00:00
abstract::Prognostic blood biomarkers for patients with uveal melanoma have not been identified. Tumor monosomy-3 is strongly associated with the development of metastatic disease. Tumor expression of human leukocyte antigen class I molecules and insulin-like growth factor (IGF)-1 receptor has also been associated with the deve...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e32835b7154
更新日期:2013-02-01 00:00:00
abstract::Malignant melanomas usually have an unfavourable prognosis and poor response to chemotherapy. Deregulation of cell proliferation, programmed cell death and intercellular interactions are among several important mechanisms that might lead to malignant transformation of melanocytes and melanoma progression. The S100A1, ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3283350554
更新日期:2010-04-01 00:00:00
abstract::There is no general consensus regarding the optimal follow-up strategy for patients with melanoma. We sought to determine the utility and cost effectiveness of radiological restaging of patients with stage IIB-IIIC melanoma at the 3-year follow-up time point. A retrospective review of 210 patients diagnosed with stage...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/CMR.0b013e3283471086
更新日期:2011-08-01 00:00:00
abstract::Large population-based studies have shown a significant association between melanoma and lymphoid neoplasia, particularly non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), that is independent of any treatment received for the initial tumour. This study examines the presentation, diagnosis, treatmen...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200110000-00012
更新日期:2001-10-01 00:00:00
abstract::Electrochemotherapy has been demonstrated to be an effective treatment for cutaneous cancers. The treatment includes administering a chemotherapeutic agent followed by electric pulses which are applied directly to the tumour. The pulses facilitate delivery of drug through the plasma membrane. Enhanced delivery is rest...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199612000-00004
更新日期:1996-12-01 00:00:00
abstract::Dermoscopy is a non-invasive technique that can be utilized for the clinical diagnosis of pigmented lesions. The aim of this study was to assess the utilization and beliefs about the usefulness of dermoscopy in the evaluation of pigmented lesions by physicians in dermatology residency programmes, and to determine the ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-200212000-00010
更新日期:2002-12-01 00:00:00
abstract::Pigmented basal cell carcinoma (PBCC) is a tumour with distinct clinical features which occasionally may be difficult to differentiate from malignant melanoma (MM). The purpose of this study was to re-examine the epiluminescence microscopy (ELM) criteria for PBCC and to determine their statistical significance in the ...
journal_title:Melanoma research
pub_type: 杂志文章
doi:10.1097/00008390-199708000-00005
更新日期:1997-08-01 00:00:00