Genetic alterations associated with multiple primary malignancies
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ABSTRACT:
PROVIDER: PRJNA693811 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Affymetrix OncoScan arrays were used to identify potential driver DNA copy number alterations and somatic mutations that promote the development of multiple primary malignancies in 26 breast cancer patients.
2021-07-14 | GSE165240 | GEO
Project description:Breast cancer (BC) patients are frequently at risk of developing other malignancies following treatment. Although studies have been conducted to elucidate the etiology of multiple primary malignancies (MPM) after a BC diagnosis, few studies have investigated other previously diagnosed primary malignancies (OPPM) before BC. Here, genome-wide profiling was used to identify potential driver DNA copy number alterations and somatic mutations that promote the development of MPMs. To compare the genomic profiles for two primary tumors (BC and OPPM) from the same patient, tumor pairs from 26 young women (≤50 years) diagnosed with one or more primary malignancies before breast cancer were analyzed. Malignant melanoma was the most frequent OPPM, followed by gynecologic- and hematologic malignancies. However, significantly more genetic alterations were detected in BC compared to the OPPM. BC also showed more genetic similarity as a group than the tumor pairs. Clonality testing showed that genetic alterations on chromosomes 1, 3, 16, and 19 were concordant in both tumors in 13 patients. TP53 mutations were also found to be prevalent in BC, MM, and HM. Although all samples were classified as genetically unstable, chromothripsis-like patterns were primarily observed in BC. Taken together, few recurrent genetic alterations were identified in both tumor pairs that can explain the development of MPMs in the same patient. However, larger studies are warranted to further investigate key driver mutations associated with MPMs.
| S-EPMC8267160 | biostudies-literature
Project description:Genetic of multiple primary cancers
| PRJNA1131824 | ENA
Project description:Immuno-Transcriptomic Profiling Identifies Actionable Alterations in Pediatric Solid Malignancies
2021-12-07 | PXD017130 | Pride
Project description:To test the long-term effects of lack of Dnmt3a on mouse HSCs, we established a cohort of lethally irradiated mice transplanted with Dnmt3a-KO or WT HSC control cells. Dnmt3a deletion in purified HSCs transplanted alone leads to an array of hematologic disorders that models the spectrum of disorders seen in human malignancies. We investigated DNA methylation alterations in disease and control mice by RRBS. We generated an average of 23.81 million reads per sample (18.97 - 31.67 million) of which an average of 18.07 million could be mapped to the mm9 genome (2.78 - 26.42 million). We achieved an average CpG coverage depth of 31.79-fold (8.09 - 47.44-fold) and average bisulfite conversion efficiency of 99.91% (99.87 - 99.95%). Reduced representation bisulfite sequencing of cells using Illumina HiSeq 2000 and 2500
2014-12-08 | E-GEOD-60264 | biostudies-arrayexpress
Project description:To test the long-term effects of lack of Dnmt3a on mouse HSCs, we established a cohort of lethally irradiated mice transplanted with Dnmt3a-KO or WT HSC control cells. Dnmt3a deletion in purified HSCs transplanted alone leads to an array of hematologic disorders that models the spectrum of disorders seen in human malignancies. We investigated DNA methylation alterations in disease and control mice by RRBS. We generated an average of 23.81 million reads per sample (18.97 - 31.67 million) of which an average of 18.07 million could be mapped to the mm9 genome (2.78 - 26.42 million). We achieved an average CpG coverage depth of 31.79-fold (8.09 - 47.44-fold) and average bisulfite conversion efficiency of 99.91% (99.87 - 99.95%).
2014-12-08 | GSE60264 | GEO
Project description:Primary myelofibrosis (PMF) is a clonal blood disorder linked to mutually exclusive mutations in JAK2, CALR, or MPL genes. To understand the epigenetic effects of these mutations, we analyzed DNA methylation (DNAm) profiles of PMF patients. Notably, no differences were found between JAK2 and CALR mutated cases, whereas MPL mutations showed distinct DNAm patterns. Further investigation in induced pluripotent stem cell (iPSC) models with JAK2 mutations revealed only a moderate link to PMF-related epigenetic changes, suggesting these alterations are not directly caused by the mutations. Additionally, PMF-associated epigenetic changes showed minimal correlation with allele burden and were largely evoked by changes in the cellular composition. When comparing PMF DNAm profiles with those from other myeloid malignancies, such as acute myeloid leukemia, juvenile myelomonocytic leukemia, and myelodysplastic syndrome, many overlapping changes were found, making it difficult to distinguish PMF based on individual CpGs. However, a PMF score created by combining five CpGs successfully differentiated PMF from other diseases in training and validation datasets. These findings demonstrate that PMF driver mutations do not directly evoke epigenetic changes. While PMF shares epigenetic changes with other myeloid malignancies, epigenetic signatures can effectively differentiate PMF from related diseases.
2025-05-07 | GSE277866 | GEO
Project description:Primary myelofibrosis (PMF) is a clonal blood disorder linked to mutually exclusive mutations in JAK2, CALR, or MPL genes. To understand the epigenetic effects of these mutations, we analyzed DNA methylation (DNAm) profiles of PMF patients. Notably, no differences were found between JAK2 and CALR mutated cases, whereas MPL mutations showed distinct DNAm patterns. Further investigation in induced pluripotent stem cell (iPSC) models with JAK2 mutations revealed only a moderate link to PMF-related epigenetic changes, suggesting these alterations are not directly caused by the mutations. Additionally, PMF-associated epigenetic changes showed minimal correlation with allele burden and were largely evoked by changes in the cellular composition. When comparing PMF DNAm profiles with those from other myeloid malignancies, such as acute myeloid leukemia, juvenile myelomonocytic leukemia, and myelodysplastic syndrome, many overlapping changes were found, making it difficult to distinguish PMF based on individual CpGs. However, a PMF score created by combining five CpGs successfully differentiated PMF from other diseases in training and validation datasets. These findings demonstrate that PMF driver mutations do not directly evoke epigenetic changes. While PMF shares epigenetic changes with other myeloid malignancies, epigenetic signatures can effectively differentiate PMF from related diseases.
2025-05-07 | GSE277841 | GEO
Project description:Background: Hodgkin lymphoma (HL) and testicular cancer (TC) survivors have an increased risk of developing second primary bowel malignancies (both colorectal cancer (CRC) and small bowel adenocarcinoma (SBA)). We aimed to determine differences in genetic characteristics of second primary bowel malignancies and primary bowel malignancies.
Methods: Copy number aberrations (CNAs) generated by low-coverage whole-genome sequencing (WGS) were collected from previous studies of second primary CRC (HL survivors, n=39), primary CRC (n=90) and primary SBA (n=14). In addition, seven new samples of second primary SBA from HL (n=3) or TC (n=5) survivors, identified in the Dutch national pathology registry (PALGA), were available for low-coverage WGS.
Results: Overall, CNA patterns observed in second primary bowel malignancies were similar to those in primary bowel malignancies. Losses of 21q22.2 were observed more frequently (p=0.057) in second primary CRC compared with primary CRC, while in second primary SBA gains of 10p15.3-15.1 and losses of 18q12.1-23 were significantly more frequent detected compared with primary SBA.
Conclusions: Second primary CRC and SBA show comparable genome wide CNAs to those in primary CRC and SBA, respectively. This suggests that part of the pathogenesis of second primary tumours in these cancer survivors is similar to those of primary CRC and SBA in general, despite the exposure to DNA damaging treatments received for earlier HL and TC.
| EGAS00001005940 | EGA
Project description:Within the frame of inherited cancer predisposition, single gene carriers of pathogenic variants (PVs) have been extensively represented in the literature, whereas the oligogenic coinheritance of heterozygous PVs in cancer-related genes is a poorly studied event. Currently, due to the increment of cancer survivors, the probability of presenting multiple primary cancers (MPC) is higher. This study included MPC patients ≤45 years without known PVs in common cancer predisposition genes. We used whole exome sequencing (WES) of germline and tumoral DNA, chromosomal microarray analysis (CMA) on germline DNA (patient 1-7, and patient 9-10), and karyotype of patient 8to detect variants associated with the disease. The ten patients included in the study presented a mean of 3 cancers per patient. CMA showed two microduplications and one microdeletion, while WES of the germline DNA identified 1-3 single nucleotide variants of potential interest to the disease in each patient and two additional copy number variants. Most of the identified variants were classified as variants of uncertain significance. The mapping of the germline variants into their pathways showed a possible additive effect of these as the cause of the cancer. Twelve somatic samples from 5 patients were available for sequencing. All the germline variants were also present in the somatic samples, while no second hits were identified in the same genes. The sequencing of patients with early cancers, family history and multiple tumors is already a standard of care. However, the growing evidence suggests that patient´s assessment should not stop at the identification of one PV in a cancer predisposition gene.
2024-08-29 | GSE271498 | GEO