Analysis of the DMBT1 gene in carcinomas of the respiratory tract

Abstract

Loss of chromosome 10q is a critical step during the progression and metastasis formation of lung cancer. We recently defined 3 distinct regions of allelic imbalances and considered the DMBT1 gene at 10q25‐q26 an interesting candidate for the most telomeric region. Therefore, we investigated DMBT1 in 25 cancer cell lines and 39 primary tumors of the respiratory tract. The analysis by RT‐PCR and Northern blot hybridization revealed that the gene is expressed in all tumors and cell lines and diminished in the SCLC line H187, indicating that RT‐PCR is critical when used as the single method for the evaluation of gene expression. No mutations were found by SSCP analysis of the cDNA and the partially known genomic sequence. Similarly, Southern blot hybridization was unable to detect homozygous deletions. Allelotyping of the markers D10S587, D10S1708 and D10S1723 located near or within the DMBT1 gene did not reach the peak incidence of the 3 minimally deleted regions that we recently defined. In summary, our data do not confirm previous findings reporting frequent loss of DMBT1 expression in lung cancer. However, they strengthen the notion that the responsible gene on chromosome 10q25‐q26 mediating tumor progression and metastasis formation in respiratory tract cancer remains enigmatic. Int. J. Cancer 88:71–76, 2000. © 2000 Wiley‐Liss, Inc.

Effects of Muclin (Dmbt1) deficiency on the gastrointestinal system

“…There is a large body of literature supporting an association of DMBT1 with cancer (2,5,23,26,35,37). However, other studies have failed to provide a link between DMBT1 and cancer (20,40,41). We did not find evidence that a lack of Muclin caused gastrointestinal tumors.…”

DNA ploidy and chromosomal alterations in head and neck squamous cell carcinoma

“…Gains of chromosome 7 were indicated by our case-bycase histogram analysis for pair-wise comparison of primary tumours and their corresponding lymph-node metastasis (LNM). This alteration has also frequently been found in carcinoma metastases to the brain [64]. The difference histogram suggested that overrepresentation of 7q11.2 might be particularly relevant for tumour spread of HNSCC.…”

“…Gain of 1q has been shown to be associated with the metastatic phenotype of lung SCCs and was one of the most frequent changes in metastases to the brain -in particular the region 1q21-q23 [64]. In HNSCC, this region carried many pronounced gains suggesting highcopy amplifications [9].…”

A novel member of the WD-repeat gene family, WDR11, maps to the 10q26 region and is disrupted by a chromosome translocation in human glioblastoma cells

“…Both PTEN and DMBT1 were only altered in 25 ± 30% of glioblastomas, and in a signi®cant number of tumors with heterozygous deletions of 10q, alterations in either PTEN or DMBT1 could not be found (Liu et al, 1997;Tohma et al, 1998;Maier et al, 1998;Somerville et al, 1998;von Deimling et al, 2000). This lack of mutations in these genes was also demonstrated for other tumors which show frequent loss of distal regions of 10q, such as carcinomas of the respiratory tract (Petersen et al, 2000), melanoma (Herbst et al, 1999), endometrial cancers (Simpkins et al, 1998), hepatocellular carcinomas (Fujiwara et al, 2000;Yeh et al, 2000) and prostate carcinoma (Dong et al, 1998). Since Northern blot analysis indicates that WDR11 is expressed in a wide variety of human tissues, it may be a target for inactivation in these tumors as well.…”