High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non-hodgkin's lymphoma

Carlos Aya-Bonilla, Michael R. Green, Emily Camilleri, Miles Benton, Colm Keane, Paula Marlton, Rod Lea, Maher K. Gandhi, Lyn R. Griffiths

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin's lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.

Original languageEnglish (US)
Pages (from-to)467-479
Number of pages13
JournalGenes Chromosomes and Cancer
Volume52
Issue number5
DOIs
StatePublished - May 1 2013

Fingerprint

Class 3 Receptor-Like Protein Tyrosine Phosphatases
Loss of Heterozygosity
Tumor Suppressor Genes
Non-Hodgkin's Lymphoma
Haplotypes
Follicular Lymphoma
Single Nucleotide Polymorphism
B-Lymphocytes
Alleles
Protein Tyrosine Phosphatases
Lymphoma, Large B-Cell, Diffuse
B-Cell Lymphoma
Hematologic Neoplasms
Phosphatidylinositol 3-Kinases
Exons
Down-Regulation

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non-hodgkin's lymphoma. / Aya-Bonilla, Carlos; Green, Michael R.; Camilleri, Emily; Benton, Miles; Keane, Colm; Marlton, Paula; Lea, Rod; Gandhi, Maher K.; Griffiths, Lyn R.

In: Genes Chromosomes and Cancer, Vol. 52, No. 5, 01.05.2013, p. 467-479.

Research output: Contribution to journalArticle

Aya-Bonilla, C, Green, MR, Camilleri, E, Benton, M, Keane, C, Marlton, P, Lea, R, Gandhi, MK & Griffiths, LR 2013, 'High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non-hodgkin's lymphoma', Genes Chromosomes and Cancer, vol. 52, no. 5, pp. 467-479. https://doi.org/10.1002/gcc.22044
Aya-Bonilla, Carlos ; Green, Michael R. ; Camilleri, Emily ; Benton, Miles ; Keane, Colm ; Marlton, Paula ; Lea, Rod ; Gandhi, Maher K. ; Griffiths, Lyn R. / High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non-hodgkin's lymphoma. In: Genes Chromosomes and Cancer. 2013 ; Vol. 52, No. 5. pp. 467-479.
@article{35e7f88632264bf49fee21ca58463d64,
title = "High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non-hodgkin's lymphoma",
abstract = "We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin's lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.",
author = "Carlos Aya-Bonilla and Green, {Michael R.} and Emily Camilleri and Miles Benton and Colm Keane and Paula Marlton and Rod Lea and Gandhi, {Maher K.} and Griffiths, {Lyn R.}",
year = "2013",
month = "5",
day = "1",
doi = "10.1002/gcc.22044",
language = "English (US)",
volume = "52",
pages = "467--479",
journal = "Genes Chromosomes and Cancer",
issn = "1045-2257",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non-hodgkin's lymphoma

AU - Aya-Bonilla, Carlos

AU - Green, Michael R.

AU - Camilleri, Emily

AU - Benton, Miles

AU - Keane, Colm

AU - Marlton, Paula

AU - Lea, Rod

AU - Gandhi, Maher K.

AU - Griffiths, Lyn R.

PY - 2013/5/1

Y1 - 2013/5/1

N2 - We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin's lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.

AB - We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin's lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.

UR - http://www.scopus.com/inward/record.url?scp=84875078146&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875078146&partnerID=8YFLogxK

U2 - 10.1002/gcc.22044

DO - 10.1002/gcc.22044

M3 - Article

C2 - 23341091

AN - SCOPUS:84875078146

VL - 52

SP - 467

EP - 479

JO - Genes Chromosomes and Cancer

JF - Genes Chromosomes and Cancer

SN - 1045-2257

IS - 5

ER -