Hideo Tateishi

A primary genetic map of markers for human chromosome 10

We have constructed a primary genetic map for human chromosome 10 from 13 polymorphic marker systems defining 11 loci, using a new gene mapping algorithm implemented in the computer program GMS. The loci form a continuous genetic map that spans approximately 116 cM in males and 170 cM in females. These loci provide regularly spaced anchor points for linkage studies, except for one interval that is 28 cM in males and 64 cM in females.

Loss of alleles at loci on chromosome 13 in human primary gastric cancers.

Mitotic events leading to the loss of the normal allele corresponding to a mutated gene are important for tumorigenesis in rare heritable tumors such as retinoblastoma and Wilms tumor. As reported for both colorectal and breast cancers, some common tumors seem to develop because of the same mitotic events. We examined constitutional and tumor genotypes defined by polymorphic DNA clones in 36 patients with gastric cancer. In 14 cases, constitutional heterozygosity at loci on chromosome 13 had been lost. Loss of alleles was also detected at a locus on chromosome 18 in two cases and at a locus on chromosome 17 in one case. The frequent loss of alleles at loci on chromosome 13 (41%) suggests that elimination of genes on this chromosome may be of importance in the tumorigenesis of human primary gastric cancers.

Combined hepatocellular/cholangiocellular carcinoma with sarcomatoid features: genetic analysis for histogenesis

The histogenesis of sarcomatoid transformation in hepatocellular carcinomas (HCCs) and cholangiocellular carcinomas (CCCs) remains unclear. In the current case, microsatellite loss of heterozygosity (LOH) assay and mutational analysis of the p53 gene with immunohistochemical examination were performed to investigate the histogenesis of each component. The tumor was composed of two parts: one part comprised poorly differentiated HCC (HCC portion), while the other part included undifferentiated, sarcomatoid HCC and CCC (combined portion). LOH at D8S555 was detected in both portions. 1-bp cytosine was deleted at codon 241 of exon 7 of the p53 gene in the combined portion. Immunohistochemically, p53 accumulated in the nuclei of undifferentiated, sarcomatoid HCC and CCC cells, suggesting that the p53 gene mutation might be common in these components. These results support the hypothesis that undifferentiated, sarcomatoid HCC and CCC could be offspring from the original HCC.

Isolation of DNA clones revealing restriction fragment length polymorphisms in the human genome

SummaryA recombinant human DNA library was constructed using pUC 18 as the cloning vector. Plasmid DNA isolated from a small scale culture was used as the hybridization probe; many recombinant clones could be easily tested for their ability to detect restriction fragment length polymorphisms (RFLPs). Forty-five arbitrary single copy DNA fragments were isolated from this library and five clones revealed RFLPs. Probe OS-5 had three alleles and probe OS-7, which detected insertion/deletion polymorphisms, had several alleles.Apart from these clones, two polymorphic DNA fragments were isolated from the pBR322 plasmid library and another two from the Charon 4A phage library. Although only four restriction enzymes were employed to detect polymorphisms, the efficiency of detecting polymorphisms was reasonable.These nine clones will serve as useful markers for linkage studies.

Close linkage of MEN2A with RBP3 locus in Japanese kindreds

SummaryThe gene responsible for multiple endocrine neoplasia type 2A (MEN2A) has recently been assigned to the pericentromeric region of chromsome 10 in European Caucasian kindreds by linkage analysis using a DNA marker, interstitial retinol-binding protein 3 (RBP3). We have found tight linkage between the MEN2A and RBP3 loci in Japanese MEN2A kindreds. The maximum lod score is 5.19 at a recombination fraction of 0.00. This result suggests that mutation of a certain gene close to RBP3 is responsible for MEN2A irrespective of ethnic backgrounds.

Accumulation of β-catenin in the cytoplasm and the nuclei during the early hepatic tumorigenesis

Hepatocellular carcinomas (HCCs) are thought to develop as well-differentiated tumors and progress to less-differentiated tumors. However, the genetic changes underlying the development and progression of HCCs are not well understood. Recent studies have shown frequent beta-catenin gene activation in HCCs by somatic alterations involving exon 3, resulting in the activation of the Wnt/Wingless signal transduction pathway. However, the exact process in which activation of Wnt/Wingless signal transduction pathway occurs during hepatic tumorigenesis remains to be elucidated. The aim of the present study was to investigate at what stage of hepatocellular tumorigenesis this pathway was activated. Altered expression of beta-catenin was investigated immunohistochemically with special reference to the grade of histological differentiation in 41 HCCs and eight dysplastic nodules. Mutational analysis of the beta-catenin gene with single-strand conformation polymorphism method and polymerase chain reaction amplification was related with the expression of this protein. beta-Catenin was expressed in the cytoplasm and the nuclei in three cases among eight dysplastic nodules, in four cases among 20 well differentiated HCCs, in five cases among 15 moderately differentiated HCCs, and one case among six poorly differentiated HCCs, respectively. Expression of beta-catenin in the cytoplasm and the nuclei was associated in one case with mutation and two cases without mutation for beta-catenin gene among 11 screened HCCs. It was concluded that beta-catenin was accumulated in the cytoplasm and the nuclei in pre-cancerous lesions of the liver and might contribute, at least in part, to hepatic tumorigenesis.

The zygosity determination of Japanese twins using a minisatellite core probe

SummaryHypervariable ‘minisatellite’ regions which are dispersed in the human genome show restriction fragment length polymorphisms (RFLPs) due to allelic differences in the number of tandem repeats containing the core sequence. Southern blot hybridization using minisatellite core probes produces various band patterns, which are completely individual-specific and of which few fragments are shared between two randomly selected individuals. If the band patterns are identical between twins, they must be monozygotic. We report here the use of minisatellite core probe for zygosity determination in five Japanese twin pairs and in a set of triplets.

Colonic lipoma with florid vascular proliferation and nodule-aggregating appearance related to repeated intussusception.

A unique case of repeatedly intussuscepted colonic lipoma mimicking an epithelial tumor in a 50‐year‐old man is reported. The tumor was located in the ascending colon and was approximately 5 cm in diameter. Colonoscopic and barium‐enema examinations suggested a huge epithelial tumor because of its nodule‐aggregating appearance. In contrast, computed tomography examination showed a fatty element in the core of the lesion. The biopsy specimens suggested a primary angiomatous lesion because of its pronounced vascular proliferation. Because the presumed diagnoses based on the examinations were different, the preoperative diagnosis was not confirmed. The tumor was composed of intramural lipoma with a multiple polypoid mucosa overlay. This lesion was unique in that the lipoma appeared to be within the muscularis propria and the multiple polypoid appearance of its covering mucosa. The mucosal changes including florid vascular proliferation, fibromuscular obliteration and epithelial regeneration suggested a reparative process, with ischemic damage due to the effects of intussusception being the most likely event. It should be kept in mind that even a simple lipoma can have a unique appearance reminiscent of epithelial tumor when it repeatedly experiences intussusception.

Assignment of a polymorphic locus of OS-4(D18S5) DNA segment to human chromosome region 18q21.3→qter

SummaryA polymorphic human DNA fragment, OS-4, isolated from pBR322 human genomic library was mapped to chromosome 18 using a human-mouse somatic cell hybrid panel. More precise assignment of this locus to 18q21.3→qter was made by hybridization to DNA from six cell lines containing different structural abnormalities of chromosome 18.In addition to TaqI polymorphism, it was proved that OS-4 could detect polymorphism in PstI-digested human DNA. This probe, designated as D18S5, would be a useful marker for gene mapping as well as linkage analysis of genetic diseases.

3-Dimensional Images Processed by Multislice CT was Efficacious to Determine the Suitable Hepatectomy for a Case of Liver Metastasis of Colon Cancer.

マルチスライスCTより作成した3次元画像が術式決定に有用であった大腸癌肝転移の1例を報告する. 症例は63歳の男性. 他院で下行結腸癌の手術を受け経過観察中, 肝転移を指摘され当院を受診した. 肝CT水平断像で腫瘍はS3を中心にS4に進展しており, 左葉切除が必要であると考えられた.CT肝動脈造影検査で左肝動脈は左胃動脈より分枝し, これが腫瘍に流入していることが示された.CT門脈造影検査では, 腫瘍は門脈P3本幹と離れていることが示された. 以上より左肝動脈を切離の後, 門脈P3本幹を温存したS3部分切除が妥当であると判断され, これらの画像に推奨された手術が可能であった. 近年, 低侵襲で多くの情報が得られるマルチスライスCTが普及しつつあるが, 肝臓外科領域での有用性についてはあまり報告されていない. 本症例に肝切除を行うに際して, マルチスライスCT は適切な術式の決定に有用であった.