Representative works in the field of 1) serological typing of hematopoietic tumor, 2) serum diagnosis of solid tumor, 3) tumor imaging and 4) antibody against oncogene products were introduced in this article to cover recent progress in diagnosis of cancer with mouse monoclonal antibody. In addition, points to be considered when to start producing antibodies were mentioned.

Five cancer-prone families, i.e., a colorectal cancer family, a gastric cancer family, two breast cancer families and a cancer family without organ specificity are reported, and familial clustering of cancer was investigated clinically. It was strongly suggested that familial clustering of cancer was related to genetic factors. The clinical characteristics of cancer-prone families were a familial tendency to cancer, early age of onset, an extraordinary frequency of multiple primary malignant neoplasms and an autosomal dominant mode of gentic transmission. The clinical significance of noting familial clustering of cancer is to extract groups at high risk for cancer, to detect early cancerous lesions and to make early therapeutic decisions.

Double cancers and related family histories were studied in eight patients who had developed cancers in the breasts and other organs. The incidence of double cancer among patients with breast cancer was 1.7% (8/472), and the age at first onset averaged 48. The organs involved were mainly the digestive system, thyroid and female sexual organs. The incidence of cancer was higher in the pedigree of double breast cancer patients than in those with solitary cancer. In follow-up study, it is necessary to elucidate the difference in characteristics between double and solitary breast cancer.

Sixty-six cases of multiple primary neoplasms in children in Japan were collected, including 8 cases of our own. These could be divided into 19 synchronous and 47 metachronous multiple neoplasms. Metachronous or multiple primary neoplasms comprised leukemia, osteosarcoma, mesenchymal sarcoma, epithelial carcinoma and others in contrast to synchronous neoplasms which consisted of many pairs of embryonic tumors. The presumptive factors for multiple primary neoplasms suggested radiotherapy-associated cancers in 30%, radiochemotherapy-associated in 13%, chemotherapy-associated in 34%, and genetic factor-related in 36% of cases. Chromosomal analysis was performed in 12 cases. Three of 4 leukemias revealed major karyotypic abnormalities in the leukemic cells. No 13q14, deletion was detected in 5 cases with multiple primary neoplasms developed with retinoblastoma. Frequent incidence of sister chromatid exchange (SCE) was detected in cultured fibroblasts or lymphocytes from one of 3 cases of second primary neoplasms associated with chemotherapy. The time interval between both neoplasms ranged from 2 to 15 years in the majority of cases. Chemotherapy-associated multiple primary neoplasms seemed to appear more quickly than radiotherapy-associated multiple primary neoplasms. Seven children out of 459 long-term survivors of childhood cancer developed multiple primary neoplasms during the period from 5 to 20 years after diagnosis of the first tumor at the National Cancer Center Hospital, Tokyo. The relative risk was suggested to be 14 times higher than the expected incidence of childhood cancer in Japan. Refinement of treatment, long-term monitoring and protective procedures for high-risk patients against multiple primary neoplasms are therefore warranted.

Heritable fragile sites are specific points on human chromosomes which appear as nonstaining gaps or breaks under certain physiological conditions and are inherited in a Mendelian codominant fashion. Recent findings of a correlation between fragile sites and breakpoints involved in specific chromosomal rearrangements seen in some neoplasias suggest that fragile sites may be unique sites particularly susceptible to chromosome breakage and rearrangement under in vivo physiological conditions. The majority of known fragile sites, including fragile X, are classified in the folate-sensitive group and are expressed under conditions of thymidylate stress. In thymidine-auxotrophic somatic cell hybrids constructed by cell fusion between fragile X cells and thymidylate synthase-negative mouse mutant cells, we have shown that thymidine deprivation alone can induce the expression of fragile X, suggesting that the primary DNA structure itself is responsible for its expression. Elucidation of the DNA structure of fragile sites may provide a clue to the understanding of genetic instability in the human genome and its possible involvement in cancer-specific chromosomal rearrangements.

N-myc, which has partial sequence homology to the oncogene c-myc, was isolated from human neuroblastoma cell lines. We have surveyed amplification of N-myc, clone 8 and pG21 in human neuroblastoma cell lines, xenografts and in primary tumors and found that amplification frequently occurred in tumors classified as stage III and IV. In situ hybridization studies demonstrated that in neuroblastomas, chromosome aberrations such as HSR (homogeneously staining region) and DMs (double minutes) are cytological manifestations of the amplification of these clones. The N-myc-related gene seems to contribute to cell growth or differentiation of the nerve cell and its amplification with enhanced expression promotes the progression of the tumor with poor prognosis.

Chromosome translocations found in hematologic malignant diseases are correlated with the cytologic and histologic features of the neoplastic cells as well as with clinical features, such as the patient's age, response to therapy and prognosis. Thus, the 8; 21 and 15; 17 translocations, respectively, are associated with acute myeloblastic and acute promyelocytic leukemias. Likewise, the 8q24 translocations including 8; 14, 2; 8, and 8; 22 translocations seen in Burkitt's lymphoma, and the 1; 19 and 11; 14 translocations seen associated with pre-B-cell and T-cell leukemias, respectively, are examples of similar correlations with regard to lymphoproliferative disorders. With the exception of the cases of 9; 22 (Ph1) and 11q23 translocations, each of which is found in both myeloid and lymphoid neoplasms, any one abnormality is rarely encountered in association with both categories of malignancy. Recent studies indicate that, with regard to many of the known chromosome translocations, the break occurs at a point close to the location of a specific cellular oncogene. Thus, c-myc and c-abl, which reside in 8q24 and 9q34, respectively, are known to undergo rearrangement in cases of 8q24 and 9; 22 translocations. These rearrangements have been proved to give rise to the production of an abnormal protein, which seems to cause the malignant transformation of cells with such chromosome translocations. Chromosome translocations are now believed to be directly related to oncogenesis through the mechanism of activation of the cellular proto-oncogene.

An absence of gene(s) on the Rb locus of chromosome 13 or a disturbance of its normal expression in the retinoblasts of the embryonic retina predisposes an individual to the development of retinoblastoma. Chromosome aberrations involving 13q14 comprised about 14% of newly arising germinal mutations. Chromosome analysis of retinoblastoma tumor cells revealed that the generation of an extra copy of the long arm of chromosome 1 or the short arm of chromosome 6 is an early event in many of the tumors and plays a significant role in engendering tumorigenicity of retinoblasts already having one mutation at the Rb locus.

A genetically high risk group for cancer may consist of persons with the following characteristics. Deficient or reduced capacity for repair of DNA damage, mostly occurring in patients with cancer-prone hereditary diseases, and possibly heterozygotes with the autosomal recessive genes of these diseases. The presence of chromosomal diseases with high incidence of cancer (e. g. Down's syndrome). The presence of autosomal dominantly inherited cancer-prone diseases. Efficient capacities for metabolic activation of potential carcinogens or reduced capacities for decomposition of carcinogens. Although the number of persons with a hereditary high risk may be small, heterozygotes of cancer-prone hereditary disease genes may account for a few percent of the general population. Relative risk, however, may be much lower in these heterozygotes than in patients, judging from the epidemiological data for ataxia telangiectasia and xeroderma pigmentosum. Correlation between cancer-proneness in these genetically high-risk groups for cancer and mutability in the cells originating from these persons has not been clearly demonstrated. Family studies and twin studies may provide further aspects for consideration of genetic factors.

This is a case report of intracranial multiple cavernous angioma occurred in a member of a lineage of familial cavernous angioma. This lineage had manifested multiple small angiomata in the extremities on seven members in her family. The patient, somewhat retarded 19-year-old woman, was admitted to Fukuoka University Hospital because of convulsive seizure and headache occurred several months before admission. She had a large head and her IQ was 71. Bilateral mild hearing disturbance and a vascular anomaly in the left eyeground were noted. There were multiple hypodermic nodules on four extremities. EEG showed spike and wave focus in the right parietal region with irregular background. Plain skull X-ray disclosed scattered small calcifications. CT scan revealed multiple high density areas in the bilateral cerebral hemispheres and splenium and cerebral angiograms presented avascular mass in the right parietal region. The tumor in the right parietal lobe which seemed to be epileptogenic focus and the hypodermic nodules of the upper extremities were removed. Pathological findings of intracranial mass and hypodermic nodule were similar, these were cavernous angioma. The mother and a younger brother of the patient had similar hypodermic nodules on the extremities, and brother's nodule was removed and confirmed cavernous angioma. Eight families of familial cavernous angioma were described in the literature. This presented case is a peculiar one on the view-point of occurrence in the central nervous system among the familial hypodermic manifestation on the extremities and coexistence of retinal vascular anomaly.

The development of teratomas and yolk sac tumors from displaced yolk sac is well documented in rats and mice. However, the precise mechanisms of induction and pathogeneses of these tumors still remain unknown. The present study was undertaken in order 1) to elucidate whether this phenomenon is common to all rodents, 2) to identify the origin of these tumors and 3) to explore specific chromosomal changes in yolk sac tumors. Ten benign teratomas and two malignant tumors with teratomatous elements were obtained from 33 Chinese hamsters after fetectomy, followed by displacement of yolk sac. The histological characteristics and the presence of laminin in the stroma suggested that the malignant tumors belonged to the category of yolk sac tumors. Similarities in electromicroscopic features observed in the tumor cells and the yolk sac of normal 12-day conceptuses suggested that the tumor originated from yolk sac cells. Chromosomal analyses of in vitro cell lines established from one of the yolk sac tumors disclosed that the tumors was composed of clones with an XX and XY sex chromosome constitution. The 1p + marker was identified as a consistent abnormality, which seemed to play an important role in the development of yolk sac tumors in Chinese hamsters.

In order to elucidate the mechanism responsible for ectopic hormone production in tumors, biosynthesis of ACHT and related peptides was studied in the pituitary and tumors at levels. In vitro biosynthesis of the ACTH/beta-LPH precursor directed by mRNA extracted from the pituitary and tumors showed no difference in translation products. It is highly likely, therefore, that different final products produced in the pituitary and tumors are caused by different posttranslational processing, such as proteolysis and glycosylation of translation products. The RNA blot analysis of tumors revealed mRNA identical to that of the pituitary. In certain tumors, however, there were larger or smaller mRNA hybridized with an ACTH/beta-LPH precursor probe, in addition to mRNA of normal size. Further studies with endonuclease S1 mapping have provided evidence suggesting that the larger one was probably produced by abnormal splicing of RNA precursor and that the smaller one was resulted possibly from aberrant transcription of the gene. The Southern blot analysis revealed no difference in restriction DNA fragments between the pituitary and tumors, indicating no evidence of gene rearrangement. From these studies, it is conceivable that ectopic ACTH production is resulted from abnormalities in the regulatory mechanism of gene expression. To further study the mechanism regulating the expression of the ACTH/beta-LPH precursor gene, human gene was transfected to mouse pituitary ACTH-producing adenoma cells (AtT-20) and fibroblasts (L-cell). The introduced human ACTH/beta-LPH precursor gene was expressed in AtT-20 cells and suppressed by glucocorticoids to an extent similar to the suppression of mouse gene. On the other hand, possible aberrant transcripts were observed in mouse L cells. It is likely, therefore, that there is a regulatory mechanism, probably "trans" acting, in the pituitary ACTH-producing producing cells and similar mechanism, though not identical, could be exerted in ectopic ACTH-producing tumors.