Novel regions of allelic deletion on chromosome 18p in tumors of the lung, brain and breast

Abstract

Lung cancer is now the number one cause of cancer death for both men and women. An age-adjusted analysis over the past 25 years shows that in women specifically, lung cancer incidence is on the rise. It is estimated that 10-20 genetic events including the alteration of oncogenes and tumor suppressor genes will have occurred by the time a lung tumor becomes clinically evident. In an effort to identify regions containing novel cancer genes, chromosome 18p11, a band not previously implicated in disease, was examined for loss of heterozygosity (LOH). In this study, 50 matched normal and NSCLC tumor samples were examined using six 18p11 and one 18q12.3 PCR-based polymorphic markers. In addition, LOH was examined in 29 glioblastoma pairs and 14 paired breast carcinomas. This analysis has revealed potentially two regions of LOH in 18p11 in up to 38% of the tumor samples examined. The regions of LOH identified included a 2 cm area between markers D18S59 and D18S476, and a more proximal, 25 cm region of intermediate frequency between D18S452 and D18S453. These results provide evidence for the presence of one or more potential tumor suppressor genes on the short arm of chromosome 18 which may be involved in NSCLC, brain tumors and possibly breast carcinomas as well.

Clear cell ependymoma: A clinicopathologic and radiographic analysis of 10 patients

“…DAL-1 originally was implicated in the tumorigenesis of nonsmall cell lung carcinoma and subsequently has been associated with additional malignancies, including glial tumors, meningiomas, and breast carcinoma. 21,[32][33][34] Recently, Singh et al 20 used both FISH and immunohistochemistry to evaluate 27 ependymomas for NF2/merlin and DAL-1/DAL-1 at the DNA and protein levels, respectively. They found NF2/merlin losses limited to spinal ependymomas, whereas the majority of DAL-1/DAL-1 losses were detected in intracranial lesions.…”

“…In a recent study by Singh et al, NF2 and DAL-1, two members of the protein 4.1 superfamily, were implicated in the pathogenesis of ependymomas. 20 Deletions/loss of NF2 (22q12) were encountered primarily in spinal ependymomas, whereas loss of DAL-1 (differentially expressed in adenocarcinoma of the lung), a related tumor suppressor gene on chromosome 18p11.3, 21,22 was more frequent in intracranial examples, including several pediatric tumors. 20 Here, we report the clinicopathologic and radiologic features, treatment, and outcome of 10 children with CCE.…”

Distinct chromosomal abnormality pattern in primary liver cancer of non-B, non-C patients

“…In colorectal and head and neck carcinomas, loss of 18q represents a poor prognostic marker (Jernvall et al, 1999;Pearlstein et al, 1998). In addition, the 18p11 region has been reported to contain at least two potential tumor suppressor genes implicated in lung, brain and possibly in breast cancer (Tran et al, 1998).…”

Protein 4.1B expression is induced in mammary epithelial cells during pregnancy and regulates their proliferation

“…Protein 4.1B is a brain-enriched ortholog of 4.1R that localizes to points of cell-cell contact at the plasma membrane (Peters et al, 1998;Parra et al, 2000). Several studies have indicated that 4.1B expression is lost or reduced in numerous malignant and benign tumors, including 54% of nonsmall cell lung carcinomas (NSCLC) (Tran et al, 1999). 4.1B is also reduced in 60% of sporadic meningiomas and 30% of ependymomas (Gutmann et al, 2000;Singh et al, 2002).…”