Genomic and gene expression profiling of minute alterations of chromosome arm 1p in small-cell lung carcinoma cells

L. J. Henderson, B. P. Coe, E. H L Lee, L. Girard, A. F. Gazdar, J. D. Minna, S. Lam, C. MacAulay, W. L. Lam

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Genetic alterations occurring on human chromosome arm 1p are common in many types of cancer including lung, breast, neuroblastoma, pheochromocytoma, and colorectal. The identification of tumour suppressors and oncogenes on this arm has been limited by the low resolution of current technologies for fine mapping. In order to identify genetic alterations on 1p in small-cell lung carcinoma, we developed a new resource for fine mapping segmental DNA copy number alterations. We have constructed an array of 642 ordered and fingerprint-verified bacterial artificial chromosome clones spanning the 120 megabase (Mb) 1p arm from 1p11.2 to p36.33. The 1p arm of 15 small-cell lung cancer cell lines was analysed at sub-Mb resolution using this arm-specific array. Among the genetic alterations identified, two regions of recurrent amplification emerged. They were detected in at least 45% of the samples: a 580kb region at 1p34.2-p34.3 and a 270kb region at 1p11.2. We further defined the potential importance of these genomic amplifications by analysing the RNA expression of the genes in these regions with Affymetrix oligonucleotide arrays and semiquantitative reverse transcriptase-polymerase chain reaction. Our data revealed overexpression of the genes HEYL, HPCAL4, BMP8, IPT, and RLF, coinciding with genomic amplification.

Original languageEnglish (US)
Pages (from-to)1553-1560
Number of pages8
JournalBritish Journal of Cancer
Volume92
Issue number8
DOIs
StatePublished - Apr 25 2005

Fingerprint

Small Cell Lung Carcinoma
Gene Expression Profiling
Arm
Chromosomes
Bacterial Artificial Chromosomes
Dermatoglyphics
Human Chromosomes
Pheochromocytoma
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Neuroblastoma
Oncogenes
Lung Neoplasms
Breast
Clone Cells
RNA
Technology
Gene Expression
Cell Line
DNA

Keywords

  • 1p
  • Array CGH
  • Gene expression
  • Small-cell lung carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Genomic and gene expression profiling of minute alterations of chromosome arm 1p in small-cell lung carcinoma cells. / Henderson, L. J.; Coe, B. P.; Lee, E. H L; Girard, L.; Gazdar, A. F.; Minna, J. D.; Lam, S.; MacAulay, C.; Lam, W. L.

In: British Journal of Cancer, Vol. 92, No. 8, 25.04.2005, p. 1553-1560.

Research output: Contribution to journalArticle

Henderson, L. J. ; Coe, B. P. ; Lee, E. H L ; Girard, L. ; Gazdar, A. F. ; Minna, J. D. ; Lam, S. ; MacAulay, C. ; Lam, W. L. / Genomic and gene expression profiling of minute alterations of chromosome arm 1p in small-cell lung carcinoma cells. In: British Journal of Cancer. 2005 ; Vol. 92, No. 8. pp. 1553-1560.
@article{6ca274f7f75c494699ea02242ecc1be6,
title = "Genomic and gene expression profiling of minute alterations of chromosome arm 1p in small-cell lung carcinoma cells",
abstract = "Genetic alterations occurring on human chromosome arm 1p are common in many types of cancer including lung, breast, neuroblastoma, pheochromocytoma, and colorectal. The identification of tumour suppressors and oncogenes on this arm has been limited by the low resolution of current technologies for fine mapping. In order to identify genetic alterations on 1p in small-cell lung carcinoma, we developed a new resource for fine mapping segmental DNA copy number alterations. We have constructed an array of 642 ordered and fingerprint-verified bacterial artificial chromosome clones spanning the 120 megabase (Mb) 1p arm from 1p11.2 to p36.33. The 1p arm of 15 small-cell lung cancer cell lines was analysed at sub-Mb resolution using this arm-specific array. Among the genetic alterations identified, two regions of recurrent amplification emerged. They were detected in at least 45{\%} of the samples: a 580kb region at 1p34.2-p34.3 and a 270kb region at 1p11.2. We further defined the potential importance of these genomic amplifications by analysing the RNA expression of the genes in these regions with Affymetrix oligonucleotide arrays and semiquantitative reverse transcriptase-polymerase chain reaction. Our data revealed overexpression of the genes HEYL, HPCAL4, BMP8, IPT, and RLF, coinciding with genomic amplification.",
keywords = "1p, Array CGH, Gene expression, Small-cell lung carcinoma",
author = "Henderson, {L. J.} and Coe, {B. P.} and Lee, {E. H L} and L. Girard and Gazdar, {A. F.} and Minna, {J. D.} and S. Lam and C. MacAulay and Lam, {W. L.}",
year = "2005",
month = "4",
day = "25",
doi = "10.1038/sj.bjc.6602452",
language = "English (US)",
volume = "92",
pages = "1553--1560",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - Genomic and gene expression profiling of minute alterations of chromosome arm 1p in small-cell lung carcinoma cells

AU - Henderson, L. J.

AU - Coe, B. P.

AU - Lee, E. H L

AU - Girard, L.

AU - Gazdar, A. F.

AU - Minna, J. D.

AU - Lam, S.

AU - MacAulay, C.

AU - Lam, W. L.

PY - 2005/4/25

Y1 - 2005/4/25

N2 - Genetic alterations occurring on human chromosome arm 1p are common in many types of cancer including lung, breast, neuroblastoma, pheochromocytoma, and colorectal. The identification of tumour suppressors and oncogenes on this arm has been limited by the low resolution of current technologies for fine mapping. In order to identify genetic alterations on 1p in small-cell lung carcinoma, we developed a new resource for fine mapping segmental DNA copy number alterations. We have constructed an array of 642 ordered and fingerprint-verified bacterial artificial chromosome clones spanning the 120 megabase (Mb) 1p arm from 1p11.2 to p36.33. The 1p arm of 15 small-cell lung cancer cell lines was analysed at sub-Mb resolution using this arm-specific array. Among the genetic alterations identified, two regions of recurrent amplification emerged. They were detected in at least 45% of the samples: a 580kb region at 1p34.2-p34.3 and a 270kb region at 1p11.2. We further defined the potential importance of these genomic amplifications by analysing the RNA expression of the genes in these regions with Affymetrix oligonucleotide arrays and semiquantitative reverse transcriptase-polymerase chain reaction. Our data revealed overexpression of the genes HEYL, HPCAL4, BMP8, IPT, and RLF, coinciding with genomic amplification.

AB - Genetic alterations occurring on human chromosome arm 1p are common in many types of cancer including lung, breast, neuroblastoma, pheochromocytoma, and colorectal. The identification of tumour suppressors and oncogenes on this arm has been limited by the low resolution of current technologies for fine mapping. In order to identify genetic alterations on 1p in small-cell lung carcinoma, we developed a new resource for fine mapping segmental DNA copy number alterations. We have constructed an array of 642 ordered and fingerprint-verified bacterial artificial chromosome clones spanning the 120 megabase (Mb) 1p arm from 1p11.2 to p36.33. The 1p arm of 15 small-cell lung cancer cell lines was analysed at sub-Mb resolution using this arm-specific array. Among the genetic alterations identified, two regions of recurrent amplification emerged. They were detected in at least 45% of the samples: a 580kb region at 1p34.2-p34.3 and a 270kb region at 1p11.2. We further defined the potential importance of these genomic amplifications by analysing the RNA expression of the genes in these regions with Affymetrix oligonucleotide arrays and semiquantitative reverse transcriptase-polymerase chain reaction. Our data revealed overexpression of the genes HEYL, HPCAL4, BMP8, IPT, and RLF, coinciding with genomic amplification.

KW - 1p

KW - Array CGH

KW - Gene expression

KW - Small-cell lung carcinoma

UR - http://www.scopus.com/inward/record.url?scp=18944364522&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18944364522&partnerID=8YFLogxK

U2 - 10.1038/sj.bjc.6602452

DO - 10.1038/sj.bjc.6602452

M3 - Article

C2 - 15785753

AN - SCOPUS:18944364522

VL - 92

SP - 1553

EP - 1560

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 8

ER -