Iroquois transcription factors are perturbed in diffuse intrinsic pontine glioma.

Abstract

<p>The brain cancer diffuse intrinsic pontine glioma (DIPG) is the most fatal of all cancers with a 5-year survival rate of less than 1%, meaning greater than 99% of patients diagnosed with DIPG will expire within 5 years (1). Systems-level analyses of the cancer transcriptome compared to the tissue from which it arises presents a unique opportunity to gain insights into the transcriptional behavior of each cancer and how it differs from its tissue of origin (2). In this study I used published microarray data to compare the DIPG tumor transcirptomes to that of the normal brain (3). In both datasets, I found differential expression of an Iroquois transcription factor in DIPG tumors: in one dataset, IRX2, IRX5 and IRX3 were among the most differentially expressed genes in the tumors of patients with DIPG, and in a separate dataset, IRX4 was significantly differentially expressed when compared to control brain tissues. IRX proteins may be important molecules in the biology of diffuse intrinsic pontine gliomas.</p>

IRX2 is differentially expressed in the lymph nodes of patients with metastatic breast cancer.

“…These data came to us with interest as we recently described the differential expression of IRX2, IRX3 and IRX5 in diffuse intrinsic pontine glioma 8 , an aggressive and uniformly fatal cancer of the brainstem. We have also recently described the shared differential expression of a network of genes, in both the lymph node and brain metastases of patients with metastatic breast cancer, suggesting that in humans with breast cancer, metastasis to the brain is intrinsically linked to metastasis to the lymph nodes .…”

“…We performed Kaplan-Meier survival analysis 8 in n =1764 breast cancer patients in total, to evaluate whether IRX2 tumor expression was correlated with survival outcomes in breast cancer. We observed a statistically significant correlation between primary tumor expression of IRX2 and recurrence-free survival (RFS) in patients with breast cancer (Figure 2).…”

HLF is differentially expressed in malignant mesothelioma.

“…We have previously performed systems-level analyses, comparing tumor to tissue of origin, comparing tumor to metastasis, or comparing the tumors of patients based on patient survival in cancers of the pancreas, head and neck, breasts, ovaries, brain, and gamma delta T-cells of the blood (9)(10)(11)(12)(13)(14)(15). Here, we extended our systems analysis of human cancers by comparing the transcriptomes of tumors isolated from patients diagnosed with mesothelioma with the transcriptome of healthy lung and peritoneum using published datasets (4,5).…”