Two candidate tumor suppressor genes, MEOX2 and SOSTDC1, identified in a 7p21 homozygous deletion region in a Wilms tumor.
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.
Ohshima
Junjiro
J
Research Institute for Clinical Oncology, Saitama Cancer Center, Ina, Saitama, Japan.
Haruta
Masayuki
M
Arai
Yasuhito
Y
Kasai
Fumio
F
Fujiwara
Yuiko
Y
Ariga
Tadashi
T
Okita
Hajime
H
Fukuzawa
Masahiro
M
Hata
Jun-Ichi
J
Horie
Hiroshi
H
Kaneko
Yasuhiko
Y
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D018392:Genomic Imprinting; D018398:Homeodomain Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D011506:Proteins / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics* / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; C484193:MEOX2 protein, human; D011506:Proteins; C480733:SOSTDC1 protein, human; D007335:Insulin-Like Growth Factor II