Isaac Halbrecht

Risk of malignancy and chromosomal polymorphism: a possible mechanism of association.

A significantly increased incidence of heterochromatic chromosomal variants, particularly of Ai and Cy, has been found in a group of 120 patients with malignant or premalignant diseases. People presenting with such a kind of polymorphism usually have an increased chromosomal breakage rate. Genetically increased susceptibility to breaking agents may be the unifying concept explaining the increased incidence of heterochromatic variants found in couples with sterility or abortions, in karyotypically normal malformed or retarded children, and in patients suffering from different malignant or premalignant diseases. Chromosomal imbalance is probably the basis for initiation of malignancy whose development is influenced by many different factors.

Repeated abortions and histocompatibility antigens. Can HLA antigen restricted gene dose effects influence the feto-maternal relationship?

It is suggested that the induction of cytotoxic reactions in the mother by allogeneic fetal cells is HLA antigen restricted and influenced, in certain haplotype combinations, by gene dose effects of specific HLA antigens (locus A and B), shared by the fetus and by the mother. The possibility that alloimmunization of maternal cells to fetal transplantation antigens may have beneficial or adverse effects on the fetal target cells dependent upon feto-maternal histocompatibility antigen interrelationship would provide a new approach for interpreting functional disturbances in certain cases of human pregnancy.

Aplastic anemia followed by leukemia in congenital trisomy 8 mosaicism:Ultrastructural studies of polymorphonuclear cells in peripheral blood

The case of a 40‐year‐old patient with congenital trisomy 8 and sex chromosome mosaicism is discussed. The main clinical features were: mental retardation, thick and darkly pig‐mented skin, prominent forehead, convergent strabismus, high arched palate, flexion contractures of the extremities, and numerous skeletal abnormalities. The patient developed severe aplastic anemia followed by an interim period of preleukemia which developed into acute leukemia. Electron microscope examination of the white blood cells at the stage of the aplastic anemia showed ultrastructural abnormalities similar to those observed in other genetic disorders with a predisposition to leukemia, as well as in leukemia.

On the meaning of fragile sites in cancer risk and development.

In the last few years, there has been increasing concern about the possible involvement of fragile sites in cancer risk and development. Patients with malignancies and family histories of cancer who presented with constitutional fragile sites are reported here. These findings are discussed with regard to the familial risk for cancer and the tissue specificity of the malignancy in relation to the different fragile sites. The hypothesis is advanced that these may be sites of viral DNA modification, probably representing areas where genes that are important for the metabolism of the virus are located. On the other hand, these genes may well be cellular (proto)oncogenes. We believe that fragile sites may increase the risk for cancer, not by being break-prone points at oncogene locations, but through more complex mechanisms that are not easy to predict.

49,XYYYY. A case report.

A 14‐month‐old boy with a 49, XYYYY karyotype is reported. The physical examination revealed unusual facial features, brachydactyly with clinodactyly, limitation of supination at the left elbow, and inguinal hernia. Radiological abnormalities of the skeleton and urinary tract were present, and the developmental examination showed a DQ of 70.

Human chromosome polymorphism and congenital malformations.

Several authors have suggested that heterochromatin polymorphism influences the origin and/or development of different malformations. In this investigation special consideration was given to the Ajqh+ variant. Several families with this variant are reported in which the incidence of otherwise rare malformations is surprisingly high. The possibility that the Aiqh+ variant or, more probably, interactions between all types of heterochromatin polymorphism are of pathogenetic significance is considered.

The fragile site on chromosome 16 (q21q22). Data on four new families.

SummaryThe significance of the fragile site on 16 (q21q22) has not yet been fully evaluated. New data will contribute to the understanding of this cytogenetic finding. Therefore we report on four families where a chromosome 16 with fragile site was segregating and such problems as infertility, abortions, malformations, and ancuploidy were present. The hypothesis that this fragile site is a site of viral modification (or integration?) is considered.

Cytogenetic study of patients with carcinoma of the colon and rectum: particular C-band variants as possible markers for cancer proneness

A possible involvement of chromosomal heterochromatic polymorphisms in propensity to cancer has been considered and discussed by several investigators who studied groups of patients presenting with different forms of malignancy. We report a cytogenetic study on the circulating lymphocytes of patients suffering from colorectal carcinoma, most of whom were of European origin. Significantly increased incidence of polymorphisms of chromosomes #1 and #9 was found, especially partial inversions (PI). Emphasis is given to the problem of selecting adequate controls, which must be as homogeneous as possible.

Involvement of chromosome 22 in a Merkel cell carcinoma in a patient with a previous meningioma

The relatively simple cytogenetic findings in an aggressive metastatic Merkel cell carcinoma are reported. Deletion 2p was found in 100% of the cells. Nevertheless, this was considered a secondary (metastatic?) change because the same aberration has been found in several other kinds of malignancy. The involvement of chromosome 22 [del(22q) and -22] in 85% of the cells seemed more intriguing, considering the fact that the Merkel cell carcinoma followed a previous meningioma.

A new familial "fragile site" on chromosome 16 (q23-24). Cytogenetic and clinical considerations

SummaryA new familial fragile site at 16q23-24 is documented, and the clinical and cytogenetic data on three families and some individual patients are reported. The importance of differentiating this fragile site from that recognized previously at 16q22 is pointed out.