Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Author Correction: Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis.

ABSTRACT:

SUBMITTER: Farshidfar F

PROVIDER: S-EPMC9090916 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Author Correction: Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis.

Farshidfar Farshad F Rhrissorrakrai Kahn K Levovitz Chaya C Peng Cong C Knight James J Bacchiocchi Antonella A Su Juan J Yin Mingzhu M Sznol Mario M Sznol Mario M Ariyan Stephan S Clune James J Olino Kelly K Parida Laxmi L Nikolaus Joerg J Zhang Meiling M Zhao Shuang S Wang Yan Y Huang Gang G Wan Miaojian M Li Xianan X Cao Jian J Yan Qin Q Chen Xiang X Newman Aaron M AM Halaban Ruth R

Nature communications 20220510 1

PMID: 35538087

Similar Datasets

Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis.

Project description:Acral melanoma, the most common melanoma subtype among non-White individuals, is associated with poor prognosis. However, its key molecular drivers remain obscure. Here, we perform integrative genomic and clinical profiling of acral melanomas from 104 patients treated in North America (n = 37) or China (n = 67). We find that recurrent, late-arising focal amplifications of cytoband 22q11.21 are a leading determinant of inferior survival, strongly associated with metastasis, and linked to downregulation of immunomodulatory genes associated with response to immune checkpoint blockade. Unexpectedly, LZTR1 - a known tumor suppressor in other cancers - is a key candidate oncogene in this cytoband. Silencing of LZTR1 in melanoma cell lines causes apoptotic cell death independent of major hotspot mutations or melanoma subtypes. Conversely, overexpression of LZTR1 in normal human melanocytes initiates processes associated with metastasis, including anchorage-independent growth, formation of spheroids, and an increase in MAPK and SRC activities. Our results provide insights into the etiology of acral melanoma and implicate LZTR1 as a key tumor promoter and therapeutic target.

| S-EPMC8866401 | biostudies-literature

Integrative molecular and clinical profiling of acral melanoma links focal amplification of chr22q11.21 to metastasis

Project description:Acral melanoma, the most common melanoma subtype among non-Caucasian individuals, is associated with poor prognosis. However, its key molecular drivers remain obscure. Here, we perform integrative genomic and clinical profiling of acral melanomas from a cohort of 104 patients treated in North America or China. We find that recurrent, late-arising amplifications of cytoband chr22q11.21 are a leading determinant of inferior survival, strongly associated with metastasis, and linked to downregulation of immunomodulatory genes associated with response to immune checkpoint blockade. Unexpectedly, LZTR1 – a known tumor suppressor in other cancers – is a key candidate oncogene in this cytoband. Silencing of LZTR1 in melanoma cell lines caused apoptotic cell death independent of major hotspot mutations or melanoma subtypes. Conversely, overexpression of LZTR1 in normal human melanocytes initiated processes associated with metastasis, including anchorage-independent growth, formation of spheroids, and increased levels of MAPK and SRC activities. Our results provide insights into the etiology of acral melanoma and implicate LZTR1 as a key tumor promoter and therapeutic target.

2021-12-14 | GSE189341 | GEO

Integrative molecular and clinical profiling of acral melanoma links focal amplification of chr22q11.21 to metastasis

Project description:Integrative molecular and clinical profiling of acral melanoma links focal amplification of chr22q11.21 to metastasis

| PRJNA782616 | ENA

Integrative Genomic Profiling Uncovers Therapeutic Targets of Acral Melanoma in Asian Populations.

Project description:PurposeAcral melanoma is the major subtype of melanoma seen in Asian patients with melanoma and is featured by its insidious onset and poor prognosis. The genomic study that elucidates driving mutational events is fundamental to the development of gene-targeted therapy. However, research on genomic profiles of acral melanoma in Asian patients is still sparse.Experimental designWe carried out whole-exome sequencing (WES) on 60 acral melanoma lesions (with 55 primary samples involved), targeted deep sequencing in a validation cohort of 48 cases, RNA sequencing in 37 acral melanoma samples (all from the 60 undergoing WES), and FISH in 233 acral melanoma specimens (54 of the 60 undergoing WES included). All the specimens were derived from Asian populations.ResultsBRAF, NRAS, and KIT were discerned as significantly mutated genes (SMG) in acral melanoma. The detected COSMIC signature 3 related to DNA damage repair, along with the high genomic instability score, implied corresponding pathogenesis of acral melanoma. Moreover, the copy number gains of EP300 were associated with the response of acral melanoma to targeted therapy of A485 (a p300 inhibitor) and immune checkpoint blockade treatment. In addition, the temporal order in mutational processes of the samples was reconstructed, and copy-number alterations were identified as early mutational events.ConclusionsOur study provided a detailed view of genomic instability, potential therapeutic targets, and intratumoral heterogeneity of acral melanoma, which might fuel the development of personalized strategies for treating acral melanoma in Asian populations.

| S-EPMC9359751 | biostudies-literature

Author Correction: Aneuploid embryonic stem cells drive teratoma metastasis.

Project description: Not available

| S-EPMC11480314 | biostudies-literature

FMRP ligand circZNF609 destabilizes RAC1 mRNA to reduce metastasis in acral melanoma and cutaneous melanoma.

Project description:BackgroundMelanoma is a type of malignant tumor with high aggressiveness and poor prognosis. At present, metastasis of melanoma is still an important cause of death in melanoma patients. However, the potential functions and molecular mechanisms of most circular RNAs (circRNAs) in melanoma metastasis remain unknown.MethodscircRNAs dysregulated in melanoma cell subgroups with different metastatic abilities according to a screening model based on repeated Transwell assays were identified with a circRNA array. The expression and prognostic significance of circZNF609 in skin cutaneous melanoma and acral melanoma cells and tissues were determined by qRT-PCR, nucleoplasmic separation assays and fluorescence in situ hybridization. In vitro wound healing, Transwell and 3D invasion assays were used to analyse melanoma cell metastasis ability. Tail vein injection and intrasplenic injection were used to study in vivo lung metastasis and liver metastasis, respectively. The mechanism of circZNF609 was further evaluated via RNA immunoprecipitation, RNA pull-down, silver staining, and immunofluorescence colocalization assays.ResultscircZNF609 was stably expressed at low levels in melanoma tissues and cells and was negatively correlated with Breslow depth, clinical stage and prognosis of melanoma patients. circZNF609 inhibited metastasis of acral and cutaneous melanoma in vivo and in vitro. Mechanistically, circZNF609 promoted the binding of FMRP protein and RAC1 mRNA, thereby enhancing the inhibitory effect of FMRP protein on the stability of RAC1 mRNA and ultimately inhibiting melanoma metastasis.ConclusionsOur findings revealed that circZNF609 plays a vital role in the metastasis of acral and cutaneous melanoma through the circRNF609-FMRP-RAC1 axis and indicated that circZNF609 regulates the stability of RAC1 mRNA by combining with FMRP, which might provide insight into melanoma pathogenesis and a new potential target for treatment of melanoma.

| S-EPMC9087950 | biostudies-literature

Acral Melanoma

Project description:Acral Melanoma

| PRJNA682608 | ENA

Author Correction: Ultrasensitive amplicon barcoding for next-generation sequencing facilitating sequence error and amplification-bias correction.

Project description:An amendment to this paper has been published and can be accessed via a link at the top of the paper.

| S-EPMC7538963 | biostudies-literature

Author Correction: Integrative genetic analysis illuminates ALS heritability and identifies risk genes.

Project description: Not available

| S-EPMC10696059 | biostudies-literature

Acral Melanoma

Project description:This SuperSeries is composed of the SubSeries listed below.