Two candidate tumor suppressor genes, MEOX2 and SOSTDC1, identified in a 7p21 homozygous deletion region in a Wilms tumor

Junjiro Ohshima, Masayuki Haruta, Yasuhito Arai, Fumio Kasai, Yuiko Fujiwara, Tadashi Ariga, Hajime Okita, Masahiro Fukuzawa, Jun Ichi Hata, Hiroshi Horie, Yasuhiko Kaneko

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Abstract

A SNP-based array analysis of 100 Wilms tumors (WT) from 97 patients identified 7p alterations (hemizygous and homozygous deletions and uniparental disomy) in nine tumors. The homozygous deletion (HD) region of 7p21 found in one tumor partially overlapped with another HD region reported previously, and was narrowed down to a 2.1-Mb region. Based on an expression analysis of 10 genes located in the HD region in 3 WT lines and previous studies on tumorigenic roles of MEOX2 and SOSTDC1, we further analyzed these two genes. Sequencing showed no mutation in MEOX2, but two missense mutations (L50F and Q129L) in SOSTDC1 in four tumors; L50F in two tumors was of germline origin. Expression levels (0, 1+ and 2+) of MEOX2 were lower in four tumors with 7p alterations than in 18 tumors with no 7p alterations (P = 0.017), and those of SOSTDC1 tended to be lower in five tumors with 7p alterations or SOSTDC1 mutation than in 17 tumors with no 7p alterations or SOSTDC1 mutation (P = 0.056). There were no significant differences in clinical characteristics between nine patients with 7p alterations and 88 patients with no 7p alterations; however, there was a difference in the status of IGF2 (uniparental disomy, loss of imprinting, or retention of imprinting) between the two patient groups (P = 0.028). Losses of MEOX2 and SOSTDC1 may accelerate angiogenesis and augment signals in the Wnt pathway, respectively. Both genes may be prime candidates for 7p tumor suppressor genes, which may have a role in the progression of Wilms tumorigenesis.

Original languageEnglish
Pages (from-to)1037-1050
Number of pages14
JournalGenes Chromosomes and Cancer
Volume48
Issue number12
DOIs
Publication statusPublished - 2009 Dec
Externally publishedYes

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Wilms Tumor
Tumor Suppressor Genes
Neoplasms
Uniparental Disomy
Mutation
Genes
Wnt Signaling Pathway
Missense Mutation
Single Nucleotide Polymorphism
Carcinogenesis

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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Two candidate tumor suppressor genes, MEOX2 and SOSTDC1, identified in a 7p21 homozygous deletion region in a Wilms tumor. / Ohshima, Junjiro; Haruta, Masayuki; Arai, Yasuhito; Kasai, Fumio; Fujiwara, Yuiko; Ariga, Tadashi; Okita, Hajime; Fukuzawa, Masahiro; Hata, Jun Ichi; Horie, Hiroshi; Kaneko, Yasuhiko.

In: Genes Chromosomes and Cancer, Vol. 48, No. 12, 12.2009, p. 1037-1050.

Research output: Contribution to journalArticle

Ohshima, J, Haruta, M, Arai, Y, Kasai, F, Fujiwara, Y, Ariga, T, Okita, H, Fukuzawa, M, Hata, JI, Horie, H & Kaneko, Y 2009, 'Two candidate tumor suppressor genes, MEOX2 and SOSTDC1, identified in a 7p21 homozygous deletion region in a Wilms tumor', Genes Chromosomes and Cancer, vol. 48, no. 12, pp. 1037-1050. https://doi.org/10.1002/gcc.20705
Ohshima, Junjiro ; Haruta, Masayuki ; Arai, Yasuhito ; Kasai, Fumio ; Fujiwara, Yuiko ; Ariga, Tadashi ; Okita, Hajime ; Fukuzawa, Masahiro ; Hata, Jun Ichi ; Horie, Hiroshi ; Kaneko, Yasuhiko. / Two candidate tumor suppressor genes, MEOX2 and SOSTDC1, identified in a 7p21 homozygous deletion region in a Wilms tumor. In: Genes Chromosomes and Cancer. 2009 ; Vol. 48, No. 12. pp. 1037-1050.
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abstract = "A SNP-based array analysis of 100 Wilms tumors (WT) from 97 patients identified 7p alterations (hemizygous and homozygous deletions and uniparental disomy) in nine tumors. The homozygous deletion (HD) region of 7p21 found in one tumor partially overlapped with another HD region reported previously, and was narrowed down to a 2.1-Mb region. Based on an expression analysis of 10 genes located in the HD region in 3 WT lines and previous studies on tumorigenic roles of MEOX2 and SOSTDC1, we further analyzed these two genes. Sequencing showed no mutation in MEOX2, but two missense mutations (L50F and Q129L) in SOSTDC1 in four tumors; L50F in two tumors was of germline origin. Expression levels (0, 1+ and 2+) of MEOX2 were lower in four tumors with 7p alterations than in 18 tumors with no 7p alterations (P = 0.017), and those of SOSTDC1 tended to be lower in five tumors with 7p alterations or SOSTDC1 mutation than in 17 tumors with no 7p alterations or SOSTDC1 mutation (P = 0.056). There were no significant differences in clinical characteristics between nine patients with 7p alterations and 88 patients with no 7p alterations; however, there was a difference in the status of IGF2 (uniparental disomy, loss of imprinting, or retention of imprinting) between the two patient groups (P = 0.028). Losses of MEOX2 and SOSTDC1 may accelerate angiogenesis and augment signals in the Wnt pathway, respectively. Both genes may be prime candidates for 7p tumor suppressor genes, which may have a role in the progression of Wilms tumorigenesis.",
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AU - Arai, Yasuhito

AU - Kasai, Fumio

AU - Fujiwara, Yuiko

AU - Ariga, Tadashi

AU - Okita, Hajime

AU - Fukuzawa, Masahiro

AU - Hata, Jun Ichi

AU - Horie, Hiroshi

AU - Kaneko, Yasuhiko

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N2 - A SNP-based array analysis of 100 Wilms tumors (WT) from 97 patients identified 7p alterations (hemizygous and homozygous deletions and uniparental disomy) in nine tumors. The homozygous deletion (HD) region of 7p21 found in one tumor partially overlapped with another HD region reported previously, and was narrowed down to a 2.1-Mb region. Based on an expression analysis of 10 genes located in the HD region in 3 WT lines and previous studies on tumorigenic roles of MEOX2 and SOSTDC1, we further analyzed these two genes. Sequencing showed no mutation in MEOX2, but two missense mutations (L50F and Q129L) in SOSTDC1 in four tumors; L50F in two tumors was of germline origin. Expression levels (0, 1+ and 2+) of MEOX2 were lower in four tumors with 7p alterations than in 18 tumors with no 7p alterations (P = 0.017), and those of SOSTDC1 tended to be lower in five tumors with 7p alterations or SOSTDC1 mutation than in 17 tumors with no 7p alterations or SOSTDC1 mutation (P = 0.056). There were no significant differences in clinical characteristics between nine patients with 7p alterations and 88 patients with no 7p alterations; however, there was a difference in the status of IGF2 (uniparental disomy, loss of imprinting, or retention of imprinting) between the two patient groups (P = 0.028). Losses of MEOX2 and SOSTDC1 may accelerate angiogenesis and augment signals in the Wnt pathway, respectively. Both genes may be prime candidates for 7p tumor suppressor genes, which may have a role in the progression of Wilms tumorigenesis.

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