American Association for Cancer Research
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Supplemental Figures and Tables from Mutational Landscape and Gene Expression Patterns in Adult Acute Myeloid Leukemias with Monosomy 7 as a Sole Abnormality

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posted on 2023-03-31, 00:28 authored by Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Krzysztof Mrózek, Stefano Volinia, James S. Blachly, Deedra Nicolet, Christopher Oakes, Karl Kroll, Shelley Orwick, Andrew J. Carroll, Richard M. Stone, John C. Byrd, Albert de la Chapelle, Clara D. Bloomfield

Supplementary Figure S1. Unsupervised clustering of the sole -7 AML cohort and the complete TCGA AML patient data set. Supplementary Figure S2. SMARCA2 mutations in AML patients with sole -7. Supplementary Figure S3. Heatmap depicting the differential gene expression of AML patients with sole -7. Supplementary Figure S4. Heatmap visualizing the gene ontology (GO) analyses of the predicted target genes of the miRs upregulated in AML patients with sole -7. Supplementary Figure S5. Heatmap visualizing the gene ontology (GO) analyses of the predicted target genes of the miRs downregulated in AML patients with sole -7. Tables: Supplementary Table S1. Gene mutations detected in 36 patients with acute myeloid leukemia (AML) and sole -7 (DNA sequencing of 81 genes). Supplementary Table S2. Mutation analysis in paired germline-leukemic samples of 10 sole -7 patients. Supplementary Table S3. Genes significantly downregulated in 31 AML patients with sole -7 compared with gene expression of 136 AML patients from the TCGA cohort (14) who had other chromosome abnormalities that did not include abnormalities of chromosome 7 or a complex karyotype. Supplementary Table S4. Genes significantly upregulated in 31 AML patients with sole -7 compared with gene expression of 136 AML patients from the TCGA cohort (14) who had other chromosome abnormalities that did not include abnormalities of chromosome 7 or a complex karyotype. Supplementary Table S5. MicroRNAs (miRs) significantly downregulated in 31 AML patients with sole -7 compared with gene expression of 136 AML patients from the TCGA cohort who had other chromosome abnormalities that did not include abnormalities of chromosome 7 or a complex karyotype. Supplementary Table S6. MicroRNAs (miRs) significantly upregulated in 31 AML patients with sole -7 compared with gene expression of 136 AML patients from the TCGA cohort who had other chromosome abnormalities that did not include abnormalities of chromosome 7 or a complex karyotype. Supplementary Table S7. Gene ontogeny analyses of significantly downregulated genes located on chromosome 7 in 31 AML patients with sole -7.

Funding

NCI

Coleman Leukemia Research Foundation

Pelotonia Fellowship Program

The Ohio Supercomputer Center

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ARTICLE ABSTRACT

Monosomy of chromosome 7 is the most frequent autosomal monosomy in acute myeloid leukemia (AML), where it associates with poor clinical outcomes. However, molecular features associated with this sole monosomy subtype (-7 AML), which may give insights into the basis for its poor prognosis, have not been characterized. In this study, we analyzed 36 cases of -7 AML for mutations in 81 leukemia/cancer-associated genes using a customized targeted next-generation sequencing panel (Miseq). Global gene and miRNA expression profiles were also determined using paired RNA and small RNA sequencing data. Notably, gene mutations were detected in all the major AML-associated functional groups, which include activated signaling, chromatin remodeling, cohesin complex, methylation, NPM1, spliceosome, transcription factors, and tumor suppressors. Gene mutations in the chromatin remodeling groups were relatively more frequent in patients <60 years of age, who also had less mutations in the methylation and spliceosome groups compared with patients ≥60 years of age. Novel recurrent mutational events in AML were identified in the SMARCA2 gene. In patients ≥60 years of age, the presence of spliceosome mutations associated with a lower complete remission rate (P = 0.03). RNA sequencing revealed distinct gene and miRNA expression patterns between the sole -7 and non -7 AML cases, with reduced expression, as expected, of many genes and miRNAs mapped to chromosome 7, and overexpression of ID1, MECOM, and PTPRM, among others. Overall, our findings illuminate a number of molecular features of the underlying aggressive pathobiology in -7 AML patients. Cancer Res; 77(1); 207–18. ©2016 AACR.

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    Cancer Research

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    Keywords

    BiomarkersDna Damage And RepairChromosomal translocationsHematological CancersLeukemias

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