The structures and transcripts of sixteen different cellular oncogenes (c-oncs) were studied in ten human osteosarcoma lines transplanted onto nude mice by Southern and Northern blot hybridization techniques. One osteosarcoma line (WAJI) had an amplification of c-myc gene at about ten-fold normal amount. High levels of c-myc transcripts were detected in four (MINO, OZA, SU, KiKu) of ten osteosarcoma lines. High levels of c-H-ras transcripts were also detected in four (OZA, TOMO, WAJI, SU) of ten osteosarcoma lines. Gene transcripts of c-fos were detected in only one osteosarcoma line (WAJI). Osteosarcomas containing detectable c-myc transcripts grew more rapidly in nude mice than those with undetectable c-myc transcripts. Levels of c-H-ras transcripts were apparently unrelated to the tumor growth rate.

Remarkable progresses have been made in the field of oncogenes in the last several years. More than 40 oncogenes or proto-oncogenes were identified by transfection assay and by weak homology of base sequences with known oncogenes. Many of them were shown to play a specific role in regulation of cell growth and signal transduction, but their exact roles in development and progression of human cancers are still not clear. Study of oncogenes and their expression at cellular level using immunohistochemistry and in situ hybridization will contribute to understand how oncogenes are involved in the multiple steps of carcinogenesis. In this article, application of newly established monoclonal antibodies to ras p21 for immunohistochemistry and immunoblotting analysis and possibilities of DNA analysis using formalin-fixed paraffin-embedded blocks are discussed.

The hst gene was originally identified in surgically obtained human gastric mucosae as a transforming gene which could transform NIH3T3 cells morphologically. The hst cDNA clone was synthesized from mRNA of one of the NIH3T3 transformants. A human leukocyte genomic library was screened with this cDNA clone, and an hst genomic fragment was obtained. This genomic fragment itself had transforming activity, and the protein coding sequences were proved to be completely identical to those of the cDNA clone prepared from mRNA of the NIH3T3 transformant. This fact suggests that rearrangement or other structural alterations in the coding sequence are not required for the activation of the hst gene. The predicted hst protein consists of 206 amino acids and has a significant homology (40-50%) to fibroblast growth factors and int-2 protein. They together make up a new superfamily of growth factors and transforming genes.

Recent development in microbiology and genetic engineering has provided the identification and characterization of so-called 'oncogenes'. The concept of oncogenes has much stimulated intense interest in searching the cause of uncontrolled cell growth and factors responsible for formation of tumors. Because of the fact that oncogenes were first discovered in an established cell line derived from patient with bladder tumor, the association between oncogenes and genitourinary cancer has much attention. Variety of pathways of tumor development in bladder cancer can be divided in two major forms, low grade papillary tumor and high grade infiltrating tumor. Activation and a sequence of oncogenes may be relevant to the ultimate expression of these separate pathways. Concept of initiation and promotion may also be factored into these consideration. The application of these principles to the different pathways of tumor development such as in bladder, kidney and prostate cancers, supports the concept that oncogenes may be required to production of malignant tumors. The purpose of this paper is to review recent evidence that has enhanced our understanding of the genetic basis of cancer development in the genitourinary tract cancer.

c-Hc-4 has been established and maintained for more than seven years. The hepatocellular carcinoma originated in 45-year old man with liver cirrhosis. The cell grew in vitro forming a sheet of monolayered cells and firmly attaching to the inner surface of cultured flasks. Morphologically they showed epithelial-like pattern. The doubling time was about 20 hours. Their modal chromosome number was 58. Serial heterologous transplantation in nude mice was successful. The histological finding was almost the same patterns as those in the primary tumor. The cultured cells produced alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA).

A patient with multiple myeloma (IgG, k) associated with hypertetraploid chromosomal abnormality is reported. The patient was a 62-year-old female. She was admitted to our clinic in October 6, 1982 because of lumbago and a supraorbital subcutaneous tumor. Cellulose acetate membrane electrophoresis of her serum disclosed a M-protein in the gamma-globulin, and immunoelectrophoresis showed monoclonal IgG, k type. A marrow aspirate of her sternum contained 15% myeloma cells, some of which were large, while others were atypical. A chromosomal analysis of her bone marrow revealed 34 hypertetraploid cells of 35 metaphase cells. Chemotherapy was administered without success and she died of DIC and uremia on November 11, 1982. Histologically, pleomorphic myeloma cells that contained large cells with atypical nuclei proliferated in her bone marrow.

Based on the following 3 points: 1) tumor proliferation is energy-dependent, 2) mitochondrial energy-production system is dominant for cell growth, and 3) liver mitochondria (mt) possess their own DNA and RNA synthesizing some of their own proteins including respiratory enzymes such as cytochrome oxidases, a possible relationship between mutations of mt-DNA and clinical status of cell proliferation was examined in 10 HCC patients who underwent liver resection. Mt-DNA at the cancerous and the noncancerous portions of 1g resected liver specimens were separated from the nuclear DNA, and then digested with Hinf I endonuclease. DNA filters were made of the digested mt-DNA fragments on the agarose and polyacrylamide gel. The filters were hybridized with a nick-translated 32P-labeled DNA fragments. In two cases, abnormal mt-DNA were detected. In the first case, the tumor was the massive type and grew rapidly invading the bile duct. One restriction fragment of 3.0 Kb of the cancerous and non cancerous portion became larger by 60 bp. In the second case, regarded as metachronous multicentric HCC, the second largest band of the 3.4 Kb fragment of the cancerous portion showed a wider range but not of the noncancerous portion. The former change may indicate polymorphism but the latter indicates an occurrence of the mutation of mt-DNA. Further studies are required, including examinations on the rest of mitochondrial fragments.

Familial adenomatous polyposis is rare disease, but it is considered as the most important clinical model for studying cancer control and carcinogenesis in general, by its extremely high risk for colorectal cancer as well as for malignancies of diverse organs which is transmitted by autosomal dominant mode. According to Knudson, the mutation for a dominantly inherited cancer susceptibility may be the first step in a recessive change in the tumor cell and same gene may be involved in both familial and non-familial cases of the tumor. The recent studies by Bodmer et al and by Solomon et al which reported on FAP locus in chromosome 5 and on loss of heterozygosity of this locus in the colorectal cancer have made an important break through in proving the Knudson's hypothesis. The epidemiological, clinical and pathological observations on FAP including our studies has been discussed in the view of these recent development of molecular biology.

Recent studies have demonstrated that the amount of epidermal growth factor receptor (EGF-R) is increased in squamous cell carcinoma cells and that the amino acid sequence of EGF-R shows great homology with the v-erb B transforming protein. In this study, we examined the tissue localization of EGF-R and myc oncogene product in normal squamous epithelium, dysplasia, carcinoma in situ, invasive squamous cell carcinoma of the uterine cervix and in metastatic lymph nodes by means of the avidin/biotin immunoperoxidase technique. Normal squamous epithelium was negative for EGF-R and myc product. The lesions of dysplasia and carcinoma in situ had a positive staining for EGF-R, but were still negative for myc product. There were differences in the staining intensity of EGF-R and myc product among the types of invasive carcinoma. Staining for EGF-R and myc product was negative in small cell non-keratinizing carcinoma, whereas strong staining for both EGF-R and myc product was observed in large cell non-keratinizing and keratinizing carcinoma. The intensity of positive staining for EGF-R and myc product declined in the lesions of cancer pearl. Metastatic lymph nodes were remarkably stained for EGF-R and myc product, while non-metastatic lymph nodes were negative for EGF-R and myc product. Our observations suggest that the amplified expression of EGF-R and myc product may accompany the malignant transformation of squamous epithelium of the uterine cervix, together with the metastasis.