Identification of a novel homozygous deletion region at 6q23.1 in medulloblastomas using high-resolution array: Comparative genomic hybridization analysis

Angela B Y Hui, Hirokuni Takano, Kwok Wai Lo, Wen Lin Kuo, Cleo N Y Lam, Carol Y K Tong, Qing Chang, Joe Gray, Ho Keung Ng

Research output: Contribution to journalArticle

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Abstract

Purpose: The aim of this study is to comprehensively characterize genome copy number aberrations in medulloblastomas using high-resolution array comparative genomic hybridization. Experimental Design: High-density genomic arrays containing 1,803 BAC clones were used to define recurrent chromosomal regions of gains or losses throughout the whole genome of medulloblastoma. A series of 3 medulloblastoma cell lines and 16 primary tumors were investigated. Results: The detected consistent chromosomal aberrations included gains of 1q21.3-q23.1 (36.8%), 1q32.1 (47.4%), 2p23.1-p25.3 (52.6%), 7 (57.9%), 9q34.13-q34.3 (47.4%), 17p11.2-q25.3 (89.5%), and 20q13.31-q13.33 (42.1%), as well as losses of 3q26.1 (57.9%), 4q31.23-q32.3 (42.1%), 6q23.1-25.3 (57.9%), 8p22-23.3 (79%), 10q24.32-26.2 (57.9%), and 16q23.2-q24.3 (63.2%). One of the most notable aberrations was a homozygous deletion on chromosome 6q23 in the celt line DAOY, and single copy loss on 30.3% primary tumors. Further analyses defined a 0.887 Mbp minimal region of homozygous deletion at 6q23.1 flanked by markers SHGC-14149 (6q22.33) and SHGC-110551 (6q23.1). Quantitative reverse transcription-PCR analysis showed complete loss of expression of two genes located at 6q23.1, AK091351 (hypothetical protein FLJ34032) and KIAA1913, in the cell line DAOY. mRNA levels of these genes was reduced in cell lines D283 and D384, and in 50% and 70% of primary tumors, respectively. Conclusion: Current array comparative genomic hybridization analysis generates a comprehensive pattern of chromosomal aberrations in medulloblastomas. This information will lead to a better understanding of medullobtastoma tumorigenesis. The delineated regions of gains or losses will indicate locations of medulloblastoma-associated genes. A 0.887 Mbp homozygous deletion region was newly identified at 6q23.1. Frequent detection of reduced expression of AK091351 and KIAA1913 genes implicates them as suppressors of medulloblastoma tumorigenesis.

Original languageEnglish (US)
Pages (from-to)4707-4716
Number of pages10
JournalClinical Cancer Research
Volume11
Issue number13
DOIs
StatePublished - Jul 1 2005
Externally publishedYes

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Medulloblastoma
Comparative Genomic Hybridization
Cell Line
Chromosome Aberrations
Carcinogenesis
Genome
Genes
Neoplasms
Chromosome Deletion
Reverse Transcription
Research Design
Clone Cells
Gene Expression
Polymerase Chain Reaction
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Identification of a novel homozygous deletion region at 6q23.1 in medulloblastomas using high-resolution array : Comparative genomic hybridization analysis. / Hui, Angela B Y; Takano, Hirokuni; Lo, Kwok Wai; Kuo, Wen Lin; Lam, Cleo N Y; Tong, Carol Y K; Chang, Qing; Gray, Joe; Ng, Ho Keung.

In: Clinical Cancer Research, Vol. 11, No. 13, 01.07.2005, p. 4707-4716.

Research output: Contribution to journalArticle

Hui, Angela B Y ; Takano, Hirokuni ; Lo, Kwok Wai ; Kuo, Wen Lin ; Lam, Cleo N Y ; Tong, Carol Y K ; Chang, Qing ; Gray, Joe ; Ng, Ho Keung. / Identification of a novel homozygous deletion region at 6q23.1 in medulloblastomas using high-resolution array : Comparative genomic hybridization analysis. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 13. pp. 4707-4716.
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title = "Identification of a novel homozygous deletion region at 6q23.1 in medulloblastomas using high-resolution array: Comparative genomic hybridization analysis",
abstract = "Purpose: The aim of this study is to comprehensively characterize genome copy number aberrations in medulloblastomas using high-resolution array comparative genomic hybridization. Experimental Design: High-density genomic arrays containing 1,803 BAC clones were used to define recurrent chromosomal regions of gains or losses throughout the whole genome of medulloblastoma. A series of 3 medulloblastoma cell lines and 16 primary tumors were investigated. Results: The detected consistent chromosomal aberrations included gains of 1q21.3-q23.1 (36.8{\%}), 1q32.1 (47.4{\%}), 2p23.1-p25.3 (52.6{\%}), 7 (57.9{\%}), 9q34.13-q34.3 (47.4{\%}), 17p11.2-q25.3 (89.5{\%}), and 20q13.31-q13.33 (42.1{\%}), as well as losses of 3q26.1 (57.9{\%}), 4q31.23-q32.3 (42.1{\%}), 6q23.1-25.3 (57.9{\%}), 8p22-23.3 (79{\%}), 10q24.32-26.2 (57.9{\%}), and 16q23.2-q24.3 (63.2{\%}). One of the most notable aberrations was a homozygous deletion on chromosome 6q23 in the celt line DAOY, and single copy loss on 30.3{\%} primary tumors. Further analyses defined a 0.887 Mbp minimal region of homozygous deletion at 6q23.1 flanked by markers SHGC-14149 (6q22.33) and SHGC-110551 (6q23.1). Quantitative reverse transcription-PCR analysis showed complete loss of expression of two genes located at 6q23.1, AK091351 (hypothetical protein FLJ34032) and KIAA1913, in the cell line DAOY. mRNA levels of these genes was reduced in cell lines D283 and D384, and in 50{\%} and 70{\%} of primary tumors, respectively. Conclusion: Current array comparative genomic hybridization analysis generates a comprehensive pattern of chromosomal aberrations in medulloblastomas. This information will lead to a better understanding of medullobtastoma tumorigenesis. The delineated regions of gains or losses will indicate locations of medulloblastoma-associated genes. A 0.887 Mbp homozygous deletion region was newly identified at 6q23.1. Frequent detection of reduced expression of AK091351 and KIAA1913 genes implicates them as suppressors of medulloblastoma tumorigenesis.",
author = "Hui, {Angela B Y} and Hirokuni Takano and Lo, {Kwok Wai} and Kuo, {Wen Lin} and Lam, {Cleo N Y} and Tong, {Carol Y K} and Qing Chang and Joe Gray and Ng, {Ho Keung}",
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T1 - Identification of a novel homozygous deletion region at 6q23.1 in medulloblastomas using high-resolution array

T2 - Comparative genomic hybridization analysis

AU - Hui, Angela B Y

AU - Takano, Hirokuni

AU - Lo, Kwok Wai

AU - Kuo, Wen Lin

AU - Lam, Cleo N Y

AU - Tong, Carol Y K

AU - Chang, Qing

AU - Gray, Joe

AU - Ng, Ho Keung

PY - 2005/7/1

Y1 - 2005/7/1

N2 - Purpose: The aim of this study is to comprehensively characterize genome copy number aberrations in medulloblastomas using high-resolution array comparative genomic hybridization. Experimental Design: High-density genomic arrays containing 1,803 BAC clones were used to define recurrent chromosomal regions of gains or losses throughout the whole genome of medulloblastoma. A series of 3 medulloblastoma cell lines and 16 primary tumors were investigated. Results: The detected consistent chromosomal aberrations included gains of 1q21.3-q23.1 (36.8%), 1q32.1 (47.4%), 2p23.1-p25.3 (52.6%), 7 (57.9%), 9q34.13-q34.3 (47.4%), 17p11.2-q25.3 (89.5%), and 20q13.31-q13.33 (42.1%), as well as losses of 3q26.1 (57.9%), 4q31.23-q32.3 (42.1%), 6q23.1-25.3 (57.9%), 8p22-23.3 (79%), 10q24.32-26.2 (57.9%), and 16q23.2-q24.3 (63.2%). One of the most notable aberrations was a homozygous deletion on chromosome 6q23 in the celt line DAOY, and single copy loss on 30.3% primary tumors. Further analyses defined a 0.887 Mbp minimal region of homozygous deletion at 6q23.1 flanked by markers SHGC-14149 (6q22.33) and SHGC-110551 (6q23.1). Quantitative reverse transcription-PCR analysis showed complete loss of expression of two genes located at 6q23.1, AK091351 (hypothetical protein FLJ34032) and KIAA1913, in the cell line DAOY. mRNA levels of these genes was reduced in cell lines D283 and D384, and in 50% and 70% of primary tumors, respectively. Conclusion: Current array comparative genomic hybridization analysis generates a comprehensive pattern of chromosomal aberrations in medulloblastomas. This information will lead to a better understanding of medullobtastoma tumorigenesis. The delineated regions of gains or losses will indicate locations of medulloblastoma-associated genes. A 0.887 Mbp homozygous deletion region was newly identified at 6q23.1. Frequent detection of reduced expression of AK091351 and KIAA1913 genes implicates them as suppressors of medulloblastoma tumorigenesis.

AB - Purpose: The aim of this study is to comprehensively characterize genome copy number aberrations in medulloblastomas using high-resolution array comparative genomic hybridization. Experimental Design: High-density genomic arrays containing 1,803 BAC clones were used to define recurrent chromosomal regions of gains or losses throughout the whole genome of medulloblastoma. A series of 3 medulloblastoma cell lines and 16 primary tumors were investigated. Results: The detected consistent chromosomal aberrations included gains of 1q21.3-q23.1 (36.8%), 1q32.1 (47.4%), 2p23.1-p25.3 (52.6%), 7 (57.9%), 9q34.13-q34.3 (47.4%), 17p11.2-q25.3 (89.5%), and 20q13.31-q13.33 (42.1%), as well as losses of 3q26.1 (57.9%), 4q31.23-q32.3 (42.1%), 6q23.1-25.3 (57.9%), 8p22-23.3 (79%), 10q24.32-26.2 (57.9%), and 16q23.2-q24.3 (63.2%). One of the most notable aberrations was a homozygous deletion on chromosome 6q23 in the celt line DAOY, and single copy loss on 30.3% primary tumors. Further analyses defined a 0.887 Mbp minimal region of homozygous deletion at 6q23.1 flanked by markers SHGC-14149 (6q22.33) and SHGC-110551 (6q23.1). Quantitative reverse transcription-PCR analysis showed complete loss of expression of two genes located at 6q23.1, AK091351 (hypothetical protein FLJ34032) and KIAA1913, in the cell line DAOY. mRNA levels of these genes was reduced in cell lines D283 and D384, and in 50% and 70% of primary tumors, respectively. Conclusion: Current array comparative genomic hybridization analysis generates a comprehensive pattern of chromosomal aberrations in medulloblastomas. This information will lead to a better understanding of medullobtastoma tumorigenesis. The delineated regions of gains or losses will indicate locations of medulloblastoma-associated genes. A 0.887 Mbp homozygous deletion region was newly identified at 6q23.1. Frequent detection of reduced expression of AK091351 and KIAA1913 genes implicates them as suppressors of medulloblastoma tumorigenesis.

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