Biology subjects

Gamis, A. S.

Publications and source records attributed to Gamis, A. S..

3 recordsLinked to original sources

bioRxiv2025

A comprehensive bulk and single-cell transcriptional atlas of pediatric leukemias

Advancements in understanding the molecular factors driving pediatric leukemias have led to an ever-increasing volume and diversity of data being generated. Recent studies are moving beyond DNA-based profiling to incorporate transcriptional data, enhancing the characterization of these cancers and informing clinical decisions. However, many existing datasets focus on specific leukemia subtypes, limiting the extraction of broader clinically relevant insights. Here, we present a comprehensive dataset of bulk and single-cell transcriptional data from 69 pediatric leukemia patients, encompassing eight leukemias. This is one of the most diverse pediatric leukemia datasets published to date. Through comparative analysis and explainable machine learning, we demonstrate the utility of these datasets in improving pediatric leukemia characterization and supporting the integration of transcriptional data into clinical testing.

cancer biology↗

bioRxiv2018

Genetic mechanisms of primary chemotherapy resistance in pediatric acute myeloid leukemia: A report from the TARGET initiative

Acute myeloid leukemias (AML) are characterized by mutations of tumor suppressor and oncogenes, involving distinct genes in adults and children. While certain mutations have been associated with the increased risk of AML relapse, the genomic landscape of primary chemotherapy resistant AML is not well defined. As part of the TARGET initiative, we performed whole-genome DNA and transcriptome (RNA and miRNA) sequencing analysis of pediatric AML with failure of induction chemotherapy. We identified at least three genetic groups of patients with induction failure, including those with NUP98 rearrangements, somatic mutations of WT1 in the absence of NUP98 mutations, and additional recurrent variants including those in KMT2C and MLLT10. Comparison of specimens before and after chemotherapy revealed distinct and invariant gene expression programs. While exhibiting overt therapy resistance, these leukemias nonetheless showed diverse forms of clonal evolution upon chemotherapy exposure. This included selection for mutant alleles of FRMD8, DHX32, PIK3R1, SHANK3, MKLN1, as well as persistence of WT1 and TP53 mutant clones, and elimination or contraction of FLT3, PTPN11, and NRAS mutant clones. These findings delineate genetic mechanisms of primary chemotherapy resistance in pediatric AML, which should inform improved approaches for its diagnosis and therapy.

cancer biology↗

bioRxiv2017

Comprehensive characterization of pediatric acute myeloid leukemia reveals novel molecular features and age-specific interactions

We present the molecular landscape of pediatric acute myeloid leukemia (AML), characterizing nearly 1,000 participants in Childrens Oncology Group (COG) AML trials. The COG/NCI TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA, miRNA sequencing and CpG methylation profiling. Validated DNA variants revealed diverse, infrequent mutations with fewer than 40 genes mutated in >2% of cases. In contrast, somatic structural variants, including novel gene fusions and focal MBNL1, ZEB2, and ELF1 deletions, were disproportionately prevalent in young as compared to adult patients. Conversely, DNMT3A and TP53 mutations, common in adults, are conspicuously absent from virtually all pediatric cases. Novel GATA2, FLT3, and CBL mutations, recurrent MYC-ITD, NRAS, KRAS, and WT1 mutations are frequent in pediatric AML. Deletions, mutations, and promoter DNA hypermethylation convergently impact Wnt signaling, Polycomb repression, innate immune cell interactions, and a cluster of zinc finger genes associated with KMT2A rearrangements. These results highlight the need for, and facilitate the development of age-tailored targeted therapies for the treatment of pediatric AML.

cancer biology↗