Denys-Drash syndrome is a rare disorder consisting of pseudohermaphrodism, Wilms' tumor and nephropathy. We describe here a boy with severe hypospadias and undescended testes, who presented with end-stage renal failure at the age of 1 year and 8 months when he was referred to our hospital. Emergency hemodialysis was performed because of oliguria, edema and severe hypertension, and then peritoneal dialysis was started. The findings of the renal biopsy showed diffuse mesangial sclerosis, consistent with the characteristic change in Denys-Drash syndrome. The analysis of WT1 gene revealed a G-to-A point mutation at 1,186 resulting in a change from Asp to Asn at 396 in exon 9. Since he had no urine output and his kidneys were not functional and in addition, patients with this mutation have been reported to have a high risk of Wilms' tumor, bilateral nephrectomy was performed. The removed kidneys showed no malignancies. Since Denys-Drash syndrome is frequently associated with Wilms' tumor, renal biopsy and gene analysis should be performed on male patients with gonadal anomaly, such as hypospadias and/or undescended testes, and proteinuria.

Recent advances in molecular analysis by polymerase chain reaction(PCR) have taken a prominent position an essential part in regeneration medicine. In hematopoietic stem cell transplantation, HLA(human leukocyte antigen) typing, assessment of graft viability/rejection (chimerism analysis), and evaluation of minimal residual disease are significant for treatment strategy. Molecular analysis will play a more important role in the diversification of transplantation methods in the future of tailor-made medicines.

Various gene information is being accumulated about the mechanisms of carcinogenesis and the characteristics of cancer cells with progress in molecular biology. However, when two or more genetic abnormalities are found in cancer, it is not easy to apply the analysis of oncogenes or tumor suppressor genes to routine laboratory examination. Further study is necessary.

When cancer patients accumulated in one pedigree, the cancer is named as familial cancer. Especially when there is strong genetic background, It is named as hereditary cancer. Most of them are caused by genetic mutation in a gene related to cancer susceptibility. The gene is classified among suppressor oncogenes, oncogenes or DNA repair genes. Although hereditary cancer is uncommon, genetic testing is very useful to confirm hereditary cancer and to diagnose it in the presymptomatic stage. On the other hand, it poses ethical problems, therefore a strategy including genetic counseling is essential.

Malignant lymphoma is a diverse group of clonal proliferative disorders derived from immature and mature lymphoid cells. Each subtype of lymphoma is defined according to a combination of morphology, immunophenotype, genetic features and clinical syndromes. Accordingly, based on our practical experience in the laboratory-oncologic point of view, the role, clinical significance, applications and laboratory issues for testing or interpretation of gene level examination in practical oncology of lymphoma are reviewed.

The diagnosis of leukemia is mainly based on chromosome analysis and genetic testing. The analysis of molecular genetics associated with chromosome abnormalities has contributed to new classifications of leukemia. The minimal residual disease(MRD) in its currently accepted application refers to low-level disease detected by quantitative PCR techniques in clinical situations. It is anticipated that efforts in characterization of molecular genetics in leukemia will ultimately translate into better clinical outcomes for patients.

With progress of human genome projects many gene mutations and their expression profiles have been much identified. Laboratory tests have become essential to achieve proper individualized medical services. In particular single nucleotide polymorphisms (SNPs) and gene expression profiles are of high interests. As one of these ongoing mmodels, we here present the SNPs of human Protein 1' also called as human Clara cell 10-kd protein (CC10). We initially found six different SNPs (A-908G, G38A, G118A, C1225T, G1226A, C4777G). For laboratory use multiplex PCR was developed to determine frequencies in normal control. The -908G and 38A genotypes were more frequent in sarcoidosis than those in controls. The SNPs of in the human protein 1 gene may be the genetic susceptibility factors for Sarcoidosis.

Genetic testings are commonly employed in various fields of clinical medicine and the test items performed at clinical laboratories are increasing rapidly in number. They are utilized to make early and/or definite diagnoses of infectious diseases, leukemia, cancers and molecular inherited diseases and also to monitor the progress of the diseases. However, these genetic testings except for infectious diseases have been developed independently at each clinical laboratory and the test results obtained at each laboratory are not always compatible each other. Under these situations it is widely expected to construct advanced genetic testing systems that can supply standardized data at any of domestic and international clinical laboratories. For the period from April, 1999 to March, 2002 three major clinical laboratories, SRL, Inc., BML, Inc. and MBC, Inc., were consigned by JBA (Japan Bioindustry Association) to collaborate in standardizing the evaluation methods for genetic testing systems among the clinical laboratories. The aim of the study is to develop the standardized genetic testing systems and to propose them as international standard operational procedures to the ISO/TC212 working group. Although one of the most important issues for standardization is the external quality assessment, they have not been carried out in reality. In this study we evaluated the difference of the genetic testing results obtained during the year of 2000 and 2001 among the clinical laboratories. The genetic testings for hematopoietic tumor, CML were selected to be evaluated since they are widely accepted as clinically useful tests.

It is widely known that patients with idiopathic pulmonary fibrosis (IPF) are frequently associated with lung cancer. Although a complication with lung cancer is an important prognostic factor for IPF, standard treatments for lung cancer cannot be given because of IPF. Especially, the administration of many anticancer agents is limited by a complication with IPF, which is recognized as a risk factor for the development of fatal lung injury in cancer chemotherapy. Epidemiological studies reveal that cigarette smoking and occupational and environmental exposure to toxic substances are common risk factors for both IPF and lung cancer. It has been assumed that metaplasia in fibrous lesions is pathologically a precancerous lesion, but it is necessary to prove several genetic abnormalities in the process of carcinogenesis in order to clarify that. Currently, several genetic abnormalities in IPF, including in p53, K-ras, FHIT and transforming growth factor (TGF)-beta 1 type II receptor, have been reported.

A 42-year-old man was diagnosed as having refractory anemia in May, 2001. He developed overt leukemia and received allogeneic bone marrow transplantation (BMT). His younger brother, a 40-year-old man, was diagnosed as having acute leukemia with trilineage myelodysplasia in November, 2001. Although he was treated with conventional chemotherapy, he failed to achieve complete remission. He also received allogeneic BMT. We suggest that environmental factors in addition to a genetic defect in the pluripotent hematopoietic stem cells may be associated with the occurrence of this familial leukemia.

To elucidate the significance of K-ras gene mutations in gastric carcinogenesis, we examined the mutations in gastric cancers and in Helicobacter pylori-associated chronic gastritis(H. pylori-CG). In gastric cancers, K-ras gene mutations were detected in intestinal type cancers, but not in diffuse type cancers. K-ras gene mutations in H. pylori-CG were significantly more frequent in gastric cancer patients than in cancer-free patients. These data suggest that K-ras gene mutations may be involved in the early stages of gastric carcinogenesis of the intestinal type. Recently, Uemura, et al. reported that H. pylori eradication suppressed gastric cancer development(Cancer Epidemiol Biomarkers Prev, 1997; N Engl J Med, 2001). Further examination is necessary to clarify the mechanism of suppression of gastric cancer development after H. pylori eradication.

It is widely accepted that carcinogenesis is a multistep process in which regulation of both cell proliferation and apoptosis is disturbed. p53, which is considered the cellular gatekeeper for growth and division, induces apoptosis. Helicobacter pylori(Hp) infection is an accepted risk factor for the development of gastric cancer, but not all infected individuals develop gastric cancer. Because CagA+ Hp induces increased cell proliferation, the CagA+ strain is believed to play an important role in the pathogenesis of gastric cancer. We have reported that p53 alteration were more frequently found in the CagA+ Hp infection in gastric cancer patients. In this chapter, we summarized recent findings of the relation among p53, CagA and cag PAI.