Tumor genetic heterogeneity analysis of chronic sun-damaged melanomas
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PROVIDER: PRJNA579371 | ENA |
REPOSITORIES: ENA
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Project description:Chronic sun-damaged (CSDhigh) melanoma represents 10-20% of cutaneous melanomas and is characterized by infrequent BRAF V600E mutations and high mutational load. However, the order of genetic events, or the extent of intra-tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. Ultra-deep targeted sequencing of 40 cancer-associated genes was performed in 73 in situ or invasive CMM, including 23 CSDhigh cases. In addition, we performed whole-exome and RNA sequencing on multiple regions of primary tumor and multiple in-transit metastases from one CSDhigh melanoma patient. We found no significant difference in mutation frequency in melanoma-related genes or in mutational load between in situ and invasive CSDhigh lesions while this difference was observed in CSDlow lesions. In addition, increased frequency of BRAF V600K, NF1 and TP53 mutations (P < 0.01, Fisher’s Exact Test) was found in CSDhigh melanomas. Sequencing of multiple specimens from one CSDhigh patient revealed strikingly limited ITH with > 95% shared mutations. Our results provide evidence that CSDhigh and CSDlow melanomas are distinct molecular entities that progress via different genetic routes.
2020-05-19 | GSE139362 | GEO
Project description:Chronic sun-damaged (CSD) melanoma represents 10%-20% of cutaneous melanomas and is characterized by infrequent BRAF V600E mutations and high mutational load. However, the order of genetic events or the extent of intra-tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. Ultra-deep targeted sequencing of 40 cancer-associated genes was performed in 72 in situ or invasive CMM, including 23 CSDhigh cases. In addition, we performed whole exome and RNA sequencing on multiple regions of primary tumor and multiple in-transit metastases from one CSDhigh melanoma patient. We found no significant difference in mutation frequency in melanoma-related genes or in mutational load between in situ and invasive CSDhigh lesions, while this difference was observed in CSDlow lesions. In addition, increased frequency of BRAF V600K, NF1, and TP53 mutations (p < .01, Fisher's exact test) was found in CSDhigh melanomas. Sequencing of multiple specimens from one CSDhigh patient revealed strikingly limited ITH with >95% shared mutations. Our results provide evidence that CSDhigh and CSDlow melanomas are distinct molecular entities that progress via different genetic routes.
| S-EPMC7217060 | biostudies-literature
Project description:Here we used a pan-cytokeratin antibody to differentiate the epidermal from dermal compartment and assayed over 18,000 RNA probes from multiple regions of interest (ROI) comparing sun protected skin, and two regions (edge and center) from AK/sun damaged skin. This allows for a trajectory from sun protected to sun damaged within an individual. Traditionally, cancer biology focusses on change within the tumor compartment for diagnosis and staging and current genetic profiling of actinic keratosis (the precursor lesion for cutaneous squamous cell carcinoma) has focused on analysis limited to whole skin or the epidermal compartment alone. Here we use spatial transcriptomics to compare and contrast the epidermal and stromal compartments from different regions of actinic keratosis and matched sun protected skin from six individuals. Our data show that the major changes in AK at the transcriptional level are evident in the dermal compartment. Sun protected skin (n=5-6 from 6 individuals for a total of 34 ROI), the center of an AK lesion (n=3 for a total of 18 ROI) and edge of the AK lesion (n=2-3 for a total of 17 ROI) representing sun-damaged skin, from six unrelated individuals, the center of an AK lesion (n=3 for a total of 18 ROI) and edge of the AK lesion (n=2-3 for a total of 17 ROI) representing sun-damaged skin, from six unrelated individuals.
2022-12-19 | GSE221000 | GEO
Project description:Here we used a pan-cytokeratin antibody to differentiate the epidermal from dermal compartment and assayed over 18,000 RNA probes from multiple regions of interest (ROI) comparing sun protected skin, and two regions (edge and center) from AK/sun damaged skin. This allows for a trajectory from sun protected to sun damaged within an individual. Traditionally, cancer biology focusses on change within the tumor compartment for diagnosis and staging and current genetic profiling of actinic keratosis (the precursor lesion for cutaneous squamous cell carcinoma) has focused on analysis limited to whole skin or the epidermal compartment alone. Here we use spatial transcriptomics to compare and contrast the epidermal and stromal compartments from different regions of actinic keratosis and matched sun protected skin from six individuals. Our data show that the major changes in AK at the transcriptional level are evident in the dermal compartment. Sun protected skin (n=5-6 from 6 individuals for a total of 34 ROI), the center of an AK lesion (n=3 for a total of 18 ROI) and edge of the AK lesion (n=2-3 for a total of 17 ROI) representing sun-damaged skin, from six unrelated individuals, the center of an AK lesion (n=3 for a total of 18 ROI) and edge of the AK lesion (n=2-3 for a total of 17 ROI) representing sun-damaged skin, from six unrelated individuals.
2022-12-19 | GSE220998 | GEO
Project description:Lack of specific markers for invasive uveal melanoma cells prevents early diagnosis of metastasis, while no systemic treatment options are available for patients with disseminated uveal melanomas. Intra-tumor heterogeneity has been recognized in numerous cancers as the main cause of metastasis development and therapy resistance. However, in uveal melanomas the specific subpopulations and their biological function which influence tumor behavior remained unknown. Here, using scRNA-seq analysis of six different primary uveal melanomas, we uncovered previously unrecognized intratumor heterogeneity. We localized diverse tumor-associated populations and transcriptional states in primary uveal melanomas. We also unraveled a gene regulatory network underlying a poor prognosis melanoma state. Heterogeneity was demonstrated in uveal melanoma tissue using the RNAscope assay. Thus, single-cell analysis offers an unprecedented view of intratumor heterogeneity in primary uveal melanoma, identified bona fide biomarkers for metastatic cells in the primary tumor, and unravel targetable modules driving metastase formation and growth, with critical implications for prognosis and therapeutic opportunity.
2021-01-25 | GSE138433 | GEO
Project description:We compared genome-wide DNA copy number alterations and mutational status in BRAF and RAS genes of 126 primary melanomas arising in four groups in which UV exposure differ: skin with (n=30), and without chronic sun damage (n=40); palms, soles and subungual (acral) sites (n=36) (which have very little sun exposure); and mucosa (n=20) (no sun exposure).
2010-06-09 | E-GEOD-2631 | biostudies-arrayexpress
Project description:We compared genome-wide DNA copy number alterations and mutational status in BRAF and RAS genes of 126 primary melanomas arising in four groups in which UV exposure differ: skin with (n=30), and without chronic sun damage (n=40); palms, soles and subungual (acral) sites (n=36) (which have very little sun exposure); and mucosa (n=20) (no sun exposure). Keywords: other
2005-11-05 | GSE2631 | GEO
Project description:Melanomas on mucosal membranes, acral skin (soles, palms, and nail bed), and skin with chronic sun-induced damage have infrequent mutations in BRAF and NRAS, genes within the mitogenactivated protein (MAP) kinase pathway commonly mutated in melanomas on intermittently sun-exposed skin. This raises the question of whether other aberrations are occurring in the MAP kinase cascade in the melanoma types with infrequent mutations of BRAF and NRAS. Oncogenic mutations in KIT were found in three of seven tumors with amplifications. Examination of all 102 primary melanomas found mutations and/or copy number increases of KIT in 39% ofmucosal, 36% of acral, and 28% of melanomas on chronically sun-damaged skin, but not in any (0%) melanomas on skin without chronic sun damage. Seventy-nine percent of tumors with mutations and 53% of tumors with multiple copies of KIT demonstrated increased KIT protein levels. KIT is an important oncogene in melanoma. Because the majority of the KIT mutations we found in melanoma also occur in imatinib-responsive cancers of other types, imatinib may offer an immediate therapeutic benefit for a significant proportion of the global melanoma burden. Keywords: melanoma, oncogene, comparative genomic hybridization, KIT
2006-09-09 | GSE4747 | GEO
Project description:Functional heterogeneity exceeds genetic heterogeneity in chronic myelomonocytic leukemia
| PRJNA464355 | ENA
Project description:Single-cell RNA-seq reveals intratumoral heterogeneity in primary uveal melanomas
| PRJNA576695 | ENA