Hemoglobin S/hemoglobin Osler: a case with 3 beta globin chains. DNA sequence (AAT) proves that Hb Osler is beta 145 Tyr-->Asn.

A 13-year-old African-American female with erythrocytosis and three different beta globins on electrophoresis beta A, beta S, and beta Osler, raised the possibility that one chromosome 11 might contain a duplicated beta globin gene, since there are normally only 2 beta globin genes. DNA sequence analysis showed GTG at codon 6 in exon 1, corresponding to Hb S and AAT at codon 145 in exon 3, indicating a substitution of Asn for Tyr. Thus, Hb Osler undergoes spontaneous post-translational deamidation, beta 145 Asn-->beta 145 Asp. Unmodified Hb Osler (Asn) co-migrates with Hb A on electrophoresis and co-elutes with Hb A on HPLC; therefore it has not been identified previously. All previous studies have incorrectly identified the mutation as being beta 145 (HC 2) Tyr-->Asp.

Congenital leukemia: report of two cases.

Congenital leukemia is a rare disease in which a leukemic process is present at birth or immediately thereafter. The majority of cases presented in the literature were reported prior to the availability of contemporary immunophenotyping methods, and lineage assignment was often made on the basis of morphology alone. Congenital leukemias may be of various lineages, although, historically, monocytic and myelomonocytic congenital leukemias appear to be the most prevalent. We present two cases of congenital leukemia with detailed immunophenotypic and cytochemical characterization. One case is of the lymphoid lineage, and the second is of myelomonocytic lineage. Neither patient displayed trisomy 21.

Saethre-Chotzen syndrome with familial translocation at chromosome 7p22.

Chromosome analysis of a male infant and his mother with Saethre-Chotzen syndrome demonstrated an apparently balanced translocation, t(2;7)(p23;p22). This association lends support to localization of the gene for Saethre-Chotzen syndrome to the 7p2 region and supports further involvement of gene(s) in the 7p22 region.

Trisomy 14 in two cases of granulosa cell tumor of the ovary.

Cytogenetic analysis of granulosa cell tumor of the ovary was performed in two patients. G-banding analysis of cells cultured 3-5 days showed that the karyotype of each tumor contained normal diploid cells as well as cells with identical aberration: trisomy 14. This is the first report of trisomy 14 in two cases of granulosa cell tumor of the ovary. Flow cytometric DNA content analysis was also performed.

Multiple chromosome aberrations in an infant with acute monoblastic leukemia.

A male infant was diagnosed at age 16 months with acute monoblastic leukemia. At diagnosis, studies of bone marrow revealed multiple chromosome aberrations: 48,XY,+8,+19,t(4;11). Chromosome studies have been repeated at remission and relapse over the course of his disease. To our knowledge, this combination of chromosome abnormalities has not been previously reported.

Identification of a specific marker chromosome early in tumor development in gamma-irradiated C57BL/6J mice.

Chromosomal changes such as aneuploidies, translocations, and gene amplification occur in many murine tumors. In this study, we have analyzed the changes in chromosomes at different stages of tumor development in C57BL/6J mice treated with gamma-irradiation or the chemical carcinogen, N-methylnitrosourea. Trisomy 15 occurred in both groups of mice regardless of inducing agent. The frequency of this event differed significantly in radiation-treated animals between stage I and stage II of the disease. A specific marker chromosome occurred only in the gamma-irradiated mice and not in the mice treated with N-methylnitrosourea. This marker consists of a translocation between chromosomes 1 and 5. It occurred in 43% of the gamma-irradiated animals at stage 1 of the disease and did not vary markedly during tumor development. In contrast, trisomy 15 increased in frequency between stages I and II of the disease in the same animals. These results suggest that the translocation event may be an early event in tumor development, whereas trisomy 15 may contribute to tumor progression.

Irradiation-induced marker chromosomes in a metastasizing murine tumor.

We have used irradiation to induce marker chromosome formation in a metastasizing murine tumor with a stable karyotype. The induced recombinant chromosomes then served to determine whether metastases were of clonal or multicellular origin. Cumulative data were obtained from four series of experiments on spontaneous metastases originating from tumors grown from irradiated cells; 20 of these metastases expressed unique chromosomal alterations consistent with a clonal origin. The majority of metastasis-derived cell populations remain stable with respect to their marker chromosomes in culture as well as in successive animal transplantation. In several instances, however, chromosomal instability was sufficient to obscure the cellular origins of individual metastases. A few metastases showed mixed chromosomal patterns initially that were consistent with multicellular origin, but repeat examinations have revealed a chromosomal instability which persisted during propagation in culture. The frequency of chromosomal recombinants in metastases from the combined series was sufficient to suggest biological and statistical significance. The morphology of recombinants was not associated with radiation dose but appeared as an apparently random response of the tumor population in different experiments. Analysis of chromosomal markers by banding techniques was performed to determine if specific chromosomes or chromosomal sites were associated with tumor cells from metastatic foci (a host-selected subpopulation with a metastatic phenotype). Our results did not reveal preferential involvement of whole chromosomes or intrachromosomal sites in recombinant formation.

A lethal presentation of de novo deletion 7q.

Deletion of 7q32----qter is a well defined syndrome which usually arises de novo. The proband we report was the result of an uncomplicated 36 week first pregnancy of non-consanguineous Oriental parents. The male infant died shortly after birth. Chromosome studies of peripheral blood and umbilical cord revealed 46,XY,del(7), apparently (q32----qter). The parents' karyotypes were normal. The observed facial structural abnormalities and hydrocephalus rather than microcephaly are in sharp contrast to the clinically described syndrome. The lethal components, absence of suprarenal glands and hydranencephaly, suggest either an unknown confounding factor or a more proximal deletion with an alternative interpretation of 7q--(q23.1----q36.1) rather than the apparent breakpoint at 7q32.

Ewing's sarcoma. Pathology, tissue culture, and cytogenetics.

The pathology, in vitro growth pattern and karyotype of an Ewing's sarcoma are reported. Light and electron microscopic findings of a talus biopsy showed pathologic characteristics typical of Ewing's sarcoma. In vitro tumor cells grew on a monolayer as small, plump, refractile cells. Tumor cells were also capable of proliferating in soft agar. Chromosome studies of cultured cells showed two consistent abnormalities: trisomy 8 and a translocation, t(11;22)(q24;q13), which has been reported previously in Ewing's sarcoma. Since this tumor is frequently difficult to distinguish from other small cell tumors, the use of several techniques (electron microscopy, tissue culture, chromosome studies) may aid the diagnosis.

Partial monosomy 13q and partial trisomy 18p: case report with necropsy findings.

We describe a stillborn female infant with severe intrauterine growth retardation and multiple congenital anomalies. She was found to have a deletion of 13q22----qter and trisomy of 18p11.2----pter, resulting from a maternal balanced translocation.

Development and progression of karyotypic variability in melanoma K1735 following X-irradiation.

Chromosomal aberrations are often assumed to be deleterious to cells. However, we have found that many metastases are populated by cells with chromosomal recombinants induced by radiation of the original tumor population. The tumor, K-1735-M2, was already capable of metastasis so that the recombinant chromosomes were not necessary for this property of the tumor. Stable recombinants, like other aberrant forms, could be disadvantageous or, alternatively, could confer selective advantage to some tumor cells. We investigated these possibilities by irradiating the parental tumor line and examining the formation and persistence of chromosomal markers in cell culture and in s.c. tumors. The karyotype of the K-1735-M2 parental tumor is composed entirely of telocentric chromosomes, and recombinant forms are relatively easy to recognize. Unstable forms of chromosome damage were lost rapidly. The frequency of stable recombinants after two weeks in culture was higher than that in tumors growing in primary inoculation sites. In contrast, secondary (spontaneous metastatic) foci showed a far greater frequency of chromosomal markers, suggesting a positive association between markers and acquisition of properties benefiting growth and metastasis.

Partial trisomy 16p due to maternal balanced translocation.

A newborn oriental male with multiple malformations was found to have partial trisomy of 16p. The mother was found to be a translocation carrier: 46,XX,t(14;16) (q32;p12).

Aberrant testicular differentiation in 46,XY gonadal dysgenesis: morphology, endocrinology, serology.

In an infant with gonadal dysgenesis and somatic anomalies, the internal and external genitalia were female but the gonads contained tubular structures suggesting male differentiation. The karyotype was 46,XY with no evidence of structural aberration or mosaicism. Hormonal metabolism and H-Y antigen expression were assayed in cultured gonadal cells. Although unable to synthesize testosterone, the cultured cells were able to convert it to dihydrotestosterone. H-Y antigen was present, perhaps at a level lower than that in cells from normal XY males. Our observations indicate that a modicum of testicular organogenesis may precede the involution that results in a streak gonad in some cases of gonadal dysgenesis.