Over-representation of specific regions of chromosome 22 in cells from human glioma correlate with resistance to 1,3-bis2-chloroethyl-1-nitrosoureaReport as inadecuate




Over-representation of specific regions of chromosome 22 in cells from human glioma correlate with resistance to 1,3-bis2-chloroethyl-1-nitrosourea - Download this document for free, or read online. Document in PDF available to download.

BMC Cancer

, 6:2

First Online: 04 January 2006Received: 07 September 2005Accepted: 04 January 2006DOI: 10.1186-1471-2407-6-2

Cite this article as: Hank, N.C., Shapiro, J.R. & Scheck, A.C. BMC Cancer 2006 6: 2. doi:10.1186-1471-2407-6-2

Abstract

BackgroundGlioblastoma multiforme is the most malignant form of brain tumor. Despite treatment including surgical resection, adjuvant chemotherapy, and radiation, these tumors typically recur. The recurrent tumor is often resistant to further therapy with the same agent, suggesting that the surviving cells that repopulate the tumor mass have an intrinsic genetic advantage. We previously demonstrated that cells selected for resistance to 1,3-bis2-chloroethyl-1-nitrosourea BCNU are near-diploid, with over-representation of part or all of chromosomes 7 and 22. While cells from untreated gliomas often have over-representation of chromosome 7, chromosome 22 is typically under-represented.

MethodsWe have analyzed cells from primary and recurrent tumors from the same patient before and after in vitro selection for resistance to clinically relevant doses of BCNU. Karyotypic analyses were done to demonstrate the genetic makeup of these cells, and fluorescent in situ hybridization analyses have defined the regions of chromosome 22 retained in these BCNU-resistant cells.

ResultsKaryotypic analyses demonstrated that cells selected for BCNU resistance were near-diploid with over-representation of chromosomes 7 and 22. In cells where whole copies of chromosome 22 were not identified, numerous fragments of this chromosome were retained and inserted into several marker and derivative chromosomes. Fluorescent in situ hybridization analyses using whole chromosome paints confirmed this finding. Additional FISH analysis using bacterial artificial chromosome probes spanning the length of chromosome 22 have allowed us to map the over-represented region to 22q12.3–13.32.

ConclusionCells selected for BCNU resistance either in vivo or in vitro retain sequences mapped to chromosome 22. The specific over-representation of sequences mapped to 22q12.3–13.32 suggest the presence of a DNA sequence important to BCNU survival and-or resistance located in this region of chromosome 22.

List of abbreviationsBCNU1,3-bis2-chloroethyl-1-nitrosourea

FISHfluorescent in situ hybridization

BACbacterial artificial chromosome

MABWaymouth MAB 87-3 medium

FCSfetal calf serum

WCPwhole chromosome paint

DAPI4-,6-Diamidino-2-phenylindole

PDGF-Bplatelet-derived growth factor, B chain

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-6-2 contains supplementary material, which is available to authorized users.

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Author: Nicole C Hank - Joan Rankin Shapiro - Adrienne C Scheck

Source: https://link.springer.com/







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