Abstract:
:Cell for cell, probably no human cancer is as aggressive as melanoma. It is among a handful of cancers whose dimensions are reported in millimeters. Tumor thickness approaching 4 mm presents a high risk of metastasis, and a diagnosis of metastatic melanoma carries with it an abysmal median survival of 6-9 mo. What features of this malignancy account for such aggressive behavior? Is it the migratory history of its cell of origin or the programmed adaptation of its differentiated progeny to environmental stress, particularly ultraviolet radiation? While the answers to these questions are far from complete, major strides have been made in our understanding of the cellular, molecular, and genetic underpinnings of melanoma. More importantly, these discoveries carry profound implications for the development of therapies focused directly at the molecular engines driving melanoma, suggesting that we may have reached the brink of an unprecedented opportunity to translate basic science into clinical advances. In this review, we attempt to summarize our current understanding of the genetics and biology of this disease, drawing from expanding genomic information and lessons from development and genetically engineered mouse models. In addition, we look forward toward how these new insights will impact on therapeutic options for metastatic melanoma in the near future.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Chin L,Garraway LA,Fisher DEdoi
10.1101/gad.1437206subject
Has Abstractpub_date
2006-08-15 00:00:00pages
2149-82issue
16eissn
0890-9369issn
1549-5477pii
20/16/2149journal_volume
20pub_type
杂志文章,评审abstract::The cytochrome P450 (CYP) gene products such as CYP3A and CYP2B are essential for the metabolism of steroid hormones and xenochemicals including prescription drugs. Nuclear receptor SXR/PXR (steroid and xenobiotic receptor/pregnenolone X receptor) has been shown both biochemically and genetically to activate CYP3A gen...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.846800
更新日期:2000-12-01 00:00:00
abstract::A cDNA library enriched for transcripts that accumulate from embryonic day 7 until day 1 posthatching was constructed from poly(A)+ RNA of chick optic lobe tissue. From this library, three recombinants were isolated that correspond to neural mRNAs appearing during the major period of synaptogenesis in the retinotectal...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.7.699
更新日期:1987-09-01 00:00:00
abstract::Netrins are secreted molecules with roles in axonal growth and angiogenesis. The Netrin receptor UNC5B is required during embryonic development for vascular patterning, suggesting that it may also contribute to postnatal and pathological angiogenesis. Here we show that unc5b is down-regulated in quiescent adult vascul...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.437807
更新日期:2007-10-01 00:00:00
abstract::The kinases ATM and ATR (Tel1 and Mec1 in the yeast Saccharomyces cerevisiae) control the response to DNA damage. We report that S. cerevisiae Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling. We show that Tel1 and Tel2 interact, and that even when Tel1 protein levels are high, this interacti...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1646208
更新日期:2008-04-01 00:00:00
abstract::Irradiation in the G1 phase of the cell cycle delays the onset of DNA synthesis and transiently inhibits the activation of replication origins in mammalian cells. It has been suggested that this inhibition is the result of the loss of torsional tension in the DNA after it has been damaged. Because irradiation causes D...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.5.554
更新日期:1994-03-01 00:00:00
abstract::RNase MRP is a ribonucleoprotein endoribonuclease that has been shown to cleave mitochondrial primer RNA sequences from a variety of sources. Most of the RNase MRP activity is found in the nucleus where it plays a role in the processing of 5.8S rRNA. A temperature-conditional point mutation in the yeast RNA component ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.21.2617
更新日期:1994-11-01 00:00:00
abstract::Intracellular heme levels must be tightly regulated to maintain proper mitochondrial respiration while minimizing toxicity, but the homeostatic mechanisms are not well understood. Here we report a novel negative feedback mechanism whereby the nuclear heme receptor Rev-erbalpha tightly controls the level of its own lig...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1825809
更新日期:2009-09-15 00:00:00
abstract::Gene duplication and divergence is a major driver in the emergence of evolutionary novelties. How variations in amino acid sequences lead to loss of ancestral activity and functional diversification of proteins is poorly understood. We used cross-species functional analysis of Drosophila Labial and its mouse HOX1 orth...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.342329.120
更新日期:2020-12-01 00:00:00
abstract::Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC-β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical p...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.302679.117
更新日期:2017-08-15 00:00:00
abstract::Signaling by the hormones brassinosteroid (BR) and gibberellin (GA) is critical to normal plant growth and development and is required for hypocotyl elongation in response to dark and elevated temperatures. Active BR signaling is essential for GA promotion of hypocotyl growth and suppresses the dwarf phenotype of GA m...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.243675.114
更新日期:2014-08-01 00:00:00
abstract::Two retrovirus promoter trap vectors (U3His and U3Neo) have been used to disrupt genes expressed in totipotent murine embryonal stem (ES) cells. Selection in L-histidinol or G418 produced clones in which the coding sequences for histidinol-dehydrogenase or neomycin-phosphotransferase were fused to sequences in or near...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.6.919
更新日期:1992-06-01 00:00:00
abstract::Changes in the pattern of gene expression play an important role in allowing cancer cells to acquire their hallmark characteristics, while genomic instability enables cells to acquire genetic alterations that promote oncogenesis. Chromatin plays central roles in both transcriptional regulation and the maintenance of g...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.255182.114
更新日期:2015-02-01 00:00:00
abstract::Fibro-adipogenic progenitors (FAPs) reside in the muscle, where they facilitate myofiber regeneration. Under normal conditions, FAPs lack myogenic potential and thus do not directly contribute to regenerated myofibers. Surprisingly, Saccone and colleagues (pp. 841-857) demonstrated that the dystrophic muscle environme...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.241182.114
更新日期:2014-04-15 00:00:00
abstract::We have studied the sequence requirements for 3'-end formation of rDNA transcripts in a cell-free system and show that the generation of correct ends of mouse pre-rRNA is brought about by a two-step process that involves a bona fide termination reaction, followed by a specific trimming of the primary transcript by 10 ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.2.224
更新日期:1989-02-01 00:00:00
abstract::Nonsense-mediated decay (NMD) is a translation-dependent RNA quality control mechanism that occurs in the cytoplasm. However, it is unknown how NMD regulates the stability of RNAs translated at the endoplasmic reticulum (ER). Here, we identify a localized NMD pathway dedicated to ER-translated mRNAs. We previously ide...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.338061.120
更新日期:2020-08-01 00:00:00
abstract::The Drosophila brain tumor (brat) gene encodes a member of the conserved NHL family of proteins, which appear to regulate differentiation and growth in a variety of organisms. One of the founding family members, Caenorhabditis elegans LIN-41, is thought to control posttranscriptional gene expression. However, the mech...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.870801
更新日期:2001-03-15 00:00:00
abstract::A major class of bacterial small RNAs (sRNAs), along with RNA-binding protein Hfq and endoribonuclease RNase E, acts on target mRNAs through base-pairing, leading to translational repression and rapid degradation of the mRNAs. In this issue of Genes & Development, Prévost and colleagues (pp. 385-396) demonstrate by us...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.2030311
更新日期:2011-02-15 00:00:00
abstract::DNA replication remains unfinished in many Drosophila polyploid cells, which harbor disproportionately fewer copies of late-replicating chromosomal regions. By analyzing paired-end high-throughput sequence data from polytene larval salivary gland cells, we define 112 underreplicated (UR) euchromatic regions 60-480 kb ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.245811.114
更新日期:2014-08-15 00:00:00
abstract::Sonic hedgehog (Shh) signaling plays a critical role during development and carcinogenesis. While Gli family members govern the transcriptional output of Shh signaling, little is known how Gli-mediated transcriptional activity is regulated. Here we identify the actin-binding protein Missing in Metastasis (MIM) as a ne...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1221804
更新日期:2004-11-15 00:00:00
abstract::We demonstrate here that the previously described bacterial promoter upstream element (UP element) consists of two distinct subsites, each of which, by itself, can bind the RNA polymerase holoenzyme alpha subunit carboxy-terminal domain (RNAP alphaCTD) and stimulate transcription. Using binding-site-selection experime...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.16.2134
更新日期:1999-08-15 00:00:00
abstract::Early endoderm formation in zebrafish requires at least three loci that function downstream of Nodal signaling but upstream of the early endodermal marker sox17: bonnie and clyde (bon), faust (fau), and casanova (cas). cas mutants show the most severe phenotype as they do not form any gut tissue and lack all sox17 exp...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.892301
更新日期:2001-06-15 00:00:00
abstract::Hedgehog signaling has been linked to cell proliferation in a variety of systems; however, its effects on the cell cycle have not been closely studied. In the vertebrate retina, Hedgehog's effects are controversial, with some reports emphasizing increased proliferation and others pointing to a role in cell cycle exit....
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.391106
更新日期:2006-11-01 00:00:00
abstract::The transcription factor NF-kappaB is a critical regulator of inflammatory and cell survival signals. Proteasomal degradation of NF-kappaB subunits plays an important role in the termination of NF-kappaB activity, and at least one of the identified ubiquitin ligases is a multimeric complex containing Copper Metabolism...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1748409
更新日期:2009-04-01 00:00:00
abstract::Start sites of DNA replication are marked by the origin recognition complex (ORC), which coordinates Mcm2-7 helicase loading to form the prereplicative complex (pre-RC). Although pre-RC assembly is well characterized in vitro, the process is poorly understood within the local chromatin environment surrounding replicat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.247924.114
更新日期:2015-01-15 00:00:00
abstract::Homeotic genes are expressed in spatially precise patterns during Drosophila development to control segmental differentiation. The Sex combs reduced (Scr) gene of the Antennapedia gene complex is involved in the determination of the labial and prothoracic segments of the embryo. To study both the wild-type pattern of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.7.716
更新日期:1987-09-01 00:00:00
abstract::Nonhomologous end joining (NHEJ) and homologous recombination (HR) represent the two major pathways of DNA double-strand break (DSB) repair in eukaryotic cells. NHEJ repairs DSBs by ligation of cognate broken ends irrespective of homologous flanking sequences, whereas HR repairs DSBs using an undamaged homologous temp...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1204304
更新日期:2004-06-01 00:00:00
abstract::Pre-rRNA transcription by RNA Polymerase I (Pol I) is very robust on active rDNA repeats. Loss of yeast Topoisomerase I (Top1) generated truncated pre-rRNA fragments, which were stabilized in strains lacking TRAMP (Trf4/Trf5-Air1/Air2-Mtr4 polyadenylation complexes) or exosome degradation activities. Loss of both Top1...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.573310
更新日期:2010-07-15 00:00:00
abstract::The myc family of cellular oncogenes encodes three highly related nuclear phosphoproteins (c-Myc, N-Myc, and L-Myc) that are believed to function as sequence-specific transcription factors capable of regulating genes important in cellular growth and differentiation. Current evidence indicates that Myc family proteins ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.8.1480
更新日期:1992-08-01 00:00:00
abstract::Binding of microRNA (miRNA) to mRNA within the RNA-induced silencing complex (RISC) leads to either translational inhibition or to destruction of the target mRNA. Both of these functions are executed by Argonaute 2 (Ago2). Using hematopoiesis in mice as a model system to study the physiological function of Ago2 in viv...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1565607
更新日期:2007-08-15 00:00:00
abstract::Constitutive activation of the Wnt/APC/beta-catenin pathway is a frequent initiating event in gastrointestinal carcinogenesis. Mutations in the Adenomatous Polyposis Coli (APC) gene up-regulate Wnt signaling by stabilizing beta-catenin and causing activation of targets important in proliferation control. Here we show ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1260605
更新日期:2005-02-01 00:00:00