Original Article

DMD and IL1RAPL1: two large adjacent genes localized within a common fragile site (FRAXC) have reduced expression in cultured brain tumors
S. McAvoy^a, S. Ganapathiraju^a, D.S. Perez^a, C.D. James^b, D.I. Smith<sup>a

a</sup>Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN,
^bDepartment of Neurosurgery, University of California, San Francisco, CA (USA)

Address of Corresponding Author

Cytogenet Genome Res 2007;119:196-203 (DOI: 10.1159/000112061)

  Abstract.

Common fragile sites (CFSs) are large regions of profound genomic instability found in all individuals. Spanning the center of the two most frequently expressed CFS regions, FRA3B (3p14.3) and FRA16D (16q23.2), are the 1.5 Mb FHIT gene and the 1.0 Mb WWOX gene. These genes are frequently deleted and/or altered in many different cancers. Both FHIT and WWOX have been demonstrated to function as tumor suppressors, both in vitro and in vivo. A number of other large CFS genes have been identified and are also frequently inactivated in multiple cancers. Based on these data, several additional very large genes were tested to determine if they were derived from within CFS regions, but DCC and RAD51L1 were not. However, the 2.0 Mb DMD gene and its immediately distal neighbor, the 1.8 Mb IL1RAPL1 gene are CFS genes contained within the FRAXC CFS region (Xp21.2p21.1). They are abundantly expressed in normal brain but were dramatically underexpressed in every brain tumor cell line and xenograft (derived from an intracranial model of glioblastoma multiforme) examined. We studied the expression of eleven other large CFS genes in the same panel of brain tumor cell lines and xenografts and found reduced expression of multiple large CFS genes in these samples. In this report we show that there is selective loss of specific large CFS genes in different cancers that does not appear to be mediated by the relative instability within different CFS regions. Further, the inactivation of multiple large CFS genes in xenografts and brain tumor cell lines may help to explain why this type of cancer is highly aggressive and associated with a poor clinical outcome.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Request reprints from David I. Smith, Ph.D.
Division of Experimental Pathology, Mayo Clinic
200 First Street, S.W., Rochester, MN 55905 (USA)
telephone: +1 507 266 0309; fax: +1 507 266 5193
e-mail: smith.david@mayo.edu

  Article Information

This work was supported by Department of Defense Grants DAMD 17-00-1-0296 (to D.I.S).

Accepted in revised form for publication by M. Schmid,: 29 October 2007.
Published online: February 01, 2008
Number of Print Pages : 8
Number of Figures : 3, Number of Tables : 3, Number of References : 57