ABSTRACT
OTX homeobox (HB) genes are expressed during embryonic morphogenesis and during the development of olfactory epithelium in adult organisms. Mutations occurring in these genes are often related to tumorigenesis in human. No data are available today regarding the possible correlation between OTX genes and tumors of the nasal cavity. The aim of this work is to understand if OTX1 and OTX2 can be considered as molecular markers in the development of nasal tumors. We selected nasal and sinonasal adenocarcinomas to investigate the expression of OTX1 and OTX2 genes through immunohistochemical and real-time PCR analyses.Both OTX1 and OTX2 were absent in all the samples of sinonasal Intestinal-Type Adenocarcinomas (ITACs). OTX1 mRNA was identified only in Non-Intestinal Type Adenocarcinomas (NITACs) while OTX2 mRNA was expressed only in Olfactory Neuroblastomas (ONs). We have demonstrated that the differential gene expression for both OTX1 and OTX2 genes might be a useful molecular marker to distinguish the different types of sinonasal tumors.
Subject(s)
Esthesioneuroblastoma, Olfactory/diagnosis , Esthesioneuroblastoma, Olfactory/genetics , Gene Expression Regulation, Developmental/genetics , Genes, Homeobox/genetics , Otx Transcription Factors/metabolism , Paranasal Sinus Neoplasms/diagnosis , Esthesioneuroblastoma, Olfactory/pathology , Humans , Paranasal Sinus Neoplasms/genetics , Paranasal Sinus Neoplasms/pathologyABSTRACT
Chronic Myeloid Leukemia (CML) is a stem cell cancer that arises when t(9;22) translocation occurs in a hematopoietic stem cells. This event results in the expression of the BCR-ABL1 fusion gene, which codes for a constitutively active tyrosine kinase that is responsible for the transformation of a HSC into a CML stem cell, which then gives rise to a clonal myeloproliferative disease. The introduction of Tyrosine Kinase Inhibitors (TKIs) has revolutionized the management of the disease. However, these drugs do not seem to be able to eradicate the malignancy. Indeed, discontinuation trials (STIM; TWISER; DADI) for those patients who achieved a profound molecular response showed 50% relapsing within 12 months. We performed a comparative analysis on 15 CML patients and one B-ALL patient, between the standard quantitative reverse-transcriptase PCR (qRT-PCR) and our genomic DNA patient-specific quantitative PCR assay (gDNA qPCR). Here we demonstrate that gDNA qPCR is better than standard qRT-PCR in disease monitoring after an average follow-up period of 200 days. Specifically, we statistically demonstrated that DNA negativity is more reliable than RNA negativity in indicating when TKIs therapy can be safely stopped.
Subject(s)
Fusion Proteins, bcr-abl/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Neoplastic Stem Cells/metabolism , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Real-Time Polymerase Chain Reaction/methods , Reverse Transcriptase Polymerase Chain Reaction/methods , Aged , DNA/genetics , Female , Follow-Up Studies , Humans , Imatinib Mesylate/pharmacology , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Male , Middle Aged , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Protein-Tyrosine Kinases/antagonists & inhibitors , RNA, Messenger/genetics , Reproducibility of Results , Treatment Outcome , Young AdultABSTRACT
INTRODUCTION: 17q21.31 microduplication syndrome is a recently described condition associated with a broad clinical spectrum, of which psychomotor delay, behavioral disorders and poor social interaction seem to be the most consistent features. Only seven patients have been reported thus far. All have behavioral disorders reminiscent of the autistic spectrum with intellectual skills ranging from normal to mild intellectual deficiency. Other features are variable with no striking common phenotypic features. CASE STUDY: Here we describe the segregation of 17q21.31 duplication in an Italian family. DISCUSSION: Clinical features and genetic data are reported, and compared with previously reported patients with 17q21.31 microduplication. A comparison of clinical manifestations between deletion and duplication syndromes of the chromosome regione is provided.
