A 2-Mb sequence-ready contig map and a novel immunoglobulin superfamily gene IGSF4 in the LOH region of chromosome 11q23.2.
Human chromosome 11q23.2 has been proposed to contain a tumor suppressor gene(s) whose deletion has been associated with cancer of the lung and breast and with neuroblastoma. To analyze the genomic structure and to isolate a candidate tumor suppressor gene from this region, we constructed a 2-Mb sequence-ready contig map using bacteriophage P1 (P1), bacterial artificial chromosome (BAC), and P1-derived artificial chromosome (PAC). The map comprises a contig of 24 overlapping P1, BAC, and PAC clones. To isolate gene fragments from the region, we performed direct cDNA library screening, exon trapping, EST mapping, and genomic sequencing using the P1, BAC, and PAC clones. Sequence analysis of 5 clones, which spans 23% (458,738 bp) of the region, and extensive gene scanning along the entire region revealed that the region is extraordinarily scarce in genes, but we identified one ubiquitously expressed novel gene and one testis-specific gene fragment. The novel gene, which we call IGSF4 (immunoglobulin superfamily 4), is transcribed into a 1.6- or 4.4-kb RNA encoding a 442-amino-acid protein. It shares strong homology with mouse IGSF-B12 and cell adhesion molecules NCAM1 and NCAM2 within their Ig-like C2-type domains. The IGSF4 gene, a novel gene that is shown to be located in the common loss of heterozygosity region, possesses a number of interesting features and may be good candidate for a tumor suppressor gene.
Gomyo
H
H
Radiobiology Division, Oncogene Division, Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Arai
Y
Y
Tanigami
A
A
Murakami
Y
Y
Hattori
M
M
Hosoda
F
F
Arai
K
K
Aikawa
Y
Y
Tsuda
H
H
Hirohashi
S
S
Asakawa
S
S
Shimizu
N
N
Soeda
E
E
Sakaki
Y
Y
Ohki
M
M
D000595:Amino Acid Sequence; D000818:Animals; D017101:Bacteriophage P1 / Q000235:genetics; D002417:Cattle; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D020451:Contig Mapping / Q000379:methods; D016147:Genes, Tumor Suppressor / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D019656:Loss of Heterozygosity / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics* / Q000302:isolation & purification; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology; D051381:Rats; D025521:Tumor Suppressor Proteins
C403514:CADM1 protein, human; C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D005819:Genetic Markers; D007136:Immunoglobulins; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins