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Downregulation of IGFBP2 is associated with resistance to IGF1R therapy in rhabdomyosarcoma

Agents targeting the insulin-like growth factor-1 receptor (IGF1R) are in clinical development, but, despite some initial success of single agents in sarcoma, response rates are low with brief durations. Thus, it is important to identify markers …

Lineage of origin in rhabdomyosarcoma informs pharmacological response

Lineage or cell of origin of cancers is often unknown and thus is not a consideration in therapeutic approaches. Alveolar rhabdomyosarcoma (aRMS) is an aggressive childhood cancer for which the cell of origin remains debated. We used conditional …

Genome-wide methylation patterns in papillary thyroid cancer are distinct based on histological subtype and tumor genotype

Aberrant DNA methylation is known to be a major factor in oncogenesis and cancer progression, but effects of methylation in papillary thyroid cancer (PTC) are not well defined. The objective of the study was to identify altered methylation patterns, …

High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias

To understand the genetic mechanisms driving variant and IGHV4-34-expressing hairy-cell leukemias, we performed whole-exome sequencing of leukemia samples from ten affected individuals, including six with matched normal samples. We identified …

NCI-60 whole exome sequencing and pharmacological CellMiner analyses

Exome sequencing provides unprecedented insights into cancer biology and pharmacological response. Here we assess these two parameters for the NCI-60, which is among the richest genomic and pharmacological publicly available cancer cell line …

Prohibitin expression is associated with high grade breast cancer but is not a driver of amplification at 17q21.33

In a study of ductal carcinoma in situ of the breast, we identified five genes at chromosome 17q21.33 that were over-expressed in high grade cases, and showed a correlation between expression and gene copy number. The aim of this study was to …

A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway

Sequence polymorphisms linked to human diseases and phenotypes in genome-wide association studies often affect noncoding regions. A SNP within an intron of the gene encoding Interferon Regulatory Factor 4 (IRF4), a transcription factor with no known …

Oncogenic ETS fusions deregulate E2F3 target genes in Ewing sarcoma and prostate cancer

Deregulated E2F transcription factor activity occurs in the vast majority of human tumors and has been solidly implicated in disturbances of cell cycle control, proliferation, and apoptosis. Aberrant E2F regulatory activity is often caused by …

Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma

Synonymous mutations, which do not alter the protein sequence, have been shown to affect protein function [Sauna ZE, Kimchi-Sarfaty C (2011) Nat Rev Genet 12(10):683-691]. However, synonymous mutations are rarely investigated in the cancer genomics …

The exomes of the NCI-60 panel: a genomic resource for cancer biology and systems pharmacology

The NCI-60 cell lines are the most frequently studied human tumor cell lines in cancer research. This panel has generated the most extensive cancer pharmacology database worldwide. In addition, these cell lines have been intensely investigated, …