Haploinsufficiency and reduced expression of genes localized to the 8p chromosomal region in human prostate tumors

Abstract

Cytogenetic and molecular studies have suggested that deletion or rearrangement of sequences that map to the short arm of chromosome 8 may be permissive for tumorigenesis in several organ systems, and in human prostate tumors in particular. In this study, we hypothesized that genes deleted for one copy and localized to the 8p chromosomal region may be transcriptionally down‐regulated or ablated in affected human prostate tumor tissues. To test this hypothesis, we used cDNA microarray analysis to determine the transcriptional profiles for 259 transcribed sequences mapping to the 8p chromosomal region for seven human prostate tumor xenografts, completely characterized for numerical and structural alterations on chromosome 8, and five normal human prostate tissues. These experiments identified 33 genes differentially expressed between normal and malignant prostate tissues, the majority of which (28/33, 85%) were transcriptionally down‐regulated in malignant compared to normal human prostate tissues. These findings, that haploinsufficiency and transcriptional down‐regulation for genes mapping to 8p are largely coincident in human prostate tumors, should provide a powerful tool for the identification of tumor‐suppressor genes associated with human prostate cancer initiation and progression. © 2003 Wiley‐Liss, Inc.

Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes

“…Indeed, in our system model, overexpression of TRAIL-R1 and -R2 was massive but only by less than 2-fold, mimicking the difference between haploinsufficiency and wild-type tumors without 8p21.3 deletions. In agreement with our results, Chaib et al 20 reported that haploinsufficiency and transcriptional down-regulation for genes mapping to 8p, including TRAIL-R1/R2, are coincident in human prostate tumors. Also in agreement with these data, several reports indicate that TRAIL can induce rejection or apoptosis of tumor cells.…”

“…[12][13][14][15][16]18,19 These findings indicate that this chromosome arm may harbor one or more haploinsufficient tumor suppressor genes. 20,21 In contrast to carcinomas and sarcomas, a detailed search for a common region of deletion across 8p has not been yet performed in B-NHL. In this report, we delineated a common region of deletion of approximately 600 kb in 8p21.3 in various B-NHL subtypes.…”

Genomic and Expression Analysis of the 8p11–12 Amplicon in Human Breast Cancer Cell Lines

“…A custom chromosome 8 cDNA array was produced at the University of Michigan Comprehensive Cancer cDNA and Affymetrix Microarray Core (24). This array consisted of PCR products amplified from 677 Research Genetics (Huntsville, AL) human cDNA clones of which the sequences mapped to chromosome 8 according to information from the National Center for Biotechnology Information Ensemble database 8 and the UCSC Genome Bioinformatics database.…”

Variation in Copy Number of MTUS1 Gene among Healthy Individuals and Cancer Patients from Gujarat

“…It is found to be ubiquitously expressed in normal tissues but transiently up-regulated during initiation of cellular quiescence and differentiation process [4] . The tumor suppression function was confirmed by mRNA expression studies in the pancreatic cancer tissues and the pancreatic cancer cell lines MIA PaCa-2, whereas the recombinant expression of MTUS1 in MIA PaCa-2 cells inhibited proliferation [13] .MTUS1 is found to be associated with disease progression in human cancers, including bladder, colorectal, oesophageal, head and neck squamous cell, hepatocellular, lung, ovarian, pancreatic, prostate and especially breast carcinomas [13][14][15][16][17] . Furthermore, it is found that MTUS1/ATIP1 is an early mediator of AT2 receptor activation.…”

“…MTUS1 is found to be associated with disease progression in human cancers, including bladder, colorectal, oesophageal, head and neck squamous cell, hepatocellular, lung, ovarian, pancreatic, prostate and especially breast carcinomas [13][14][15][16][17] . Furthermore, it is found that MTUS1/ATIP1 is an early mediator of AT2 receptor activation.…”