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Genetic Phenomena Commons

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Full-Text Articles in Genetic Phenomena

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker Aug 2021

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …


Dnmt3a Haploinsufficiency Provokes Hematologic Malignancy Of B-Lymphoid, T-Lymphoid, And Myeloid Lineage In Mice, Garland Michael Upchurch Aug 2017

Dnmt3a Haploinsufficiency Provokes Hematologic Malignancy Of B-Lymphoid, T-Lymphoid, And Myeloid Lineage In Mice, Garland Michael Upchurch

Theses & Dissertations

DNA methyltransferase 3A (DNMT3A) is a master epigenetic regulator of benign and malignant hematopoiesis. To dissect the biological consequences of homozygous and heterozygous Dnmt3a inactivation in malignant hematopoiesis, we generated Dnmt3a homozygous null (Dnmt3aΔ/Δ) and Dnmt3a heterozygous (Dnmt3a+/) mice and compared the presentations of hematologic malignancies between cohorts. Bi-allelic inactivation of Dnmt3a results in the presentation of mature lymphoid neoplasms resembling chronic lymphocytic leukemia (CLL; B220+CD19+CD5+; 88% penetrance (37/42)) and CD8+ peripheral T-cell lymphoma (PTCL; TCRβ+CD3+CD8+CD4; 40% penetrance (17/42)). …