Biomedical subjects
Publications and source records attributed to U Kristoffersson.
A patient with the typical features of the 18q- syndrome, but with the deletion restricted to the most distal part, bands q22.3----qter is reported. The cytogenetic finding is supported by a decrease in activity of the enzyme peptidase A.
An inverted tandem duplication of 1q11-q22 was found in a male infant with severely retarded psychomotor development, growth retardation, and multiple congenital malformations. Trisomy for this segment of chromosome 1 has not been previously reported.
A child with multiple anomalies, including growth retardation, a left-sided diaphragmatic hernia with lung hypoplasia, and cerebral malformations is described. Cytogenetic investigation demonstrated a deletion of the distal part of one chromosome 15, del(15)(q24qter), an aberration not previously described. Family studies revealed that the mother had a balanced translocation, t(6;15)(p25;q24). Two of her subsequent pregnancies resulted in abortions after prenatal diagnosis: one fetus was trisomic for 15q24----qter, while the other had monosomy 15q24----qter and a left-sided diaphragmatic hernia similar to the first child.
The cytogenetic findings in 70 patients with non-Hodgkin lymphoma have been correlated with tumor histopathology according to the Kiel classification. Certain chromosome aberrations displayed a nonrandom association with the grade of malignancy: 4 lymphomas out of 6 with 1p+, 5 out of 7 with del(6)(q15), 7 out of 11 with 14q+, and 5 out of 8 with +18 belonged to the high grade malignancy group, whereas 9 lymphomas out of 10 with t(14;18) were low grade malignant. Two aberration types were closely associated with specific histopathologic subtypes: t(14;18) occurred in 7 cases out of 10 in centroblastic/centrocytic (cb/cc) follicular lymphomas, and 5 cases out of 6 with i(17q) were cb or cb/cc. Although less striking, there was a tendency for del(6)(q15) to occur in cb or cb/cc lymphomas (4 cases out of 7), in contrast to only 1 case out of 5 with the more distal deletion del(6)(q21).
Cytogenetic analysis was attempted in 20 patients with Hodgkin's disease. No mitoses were found in 2 cases, normal metaphases in 7, and normal metaphases with nonclonal aberrations in 7. Of the 4 cases with clonal aberrations, one had +16 as the sole change, whereas the remaining tumors had multiple numerical and structural changes.
The karyotypic abnormalities and clinical data on three patients in whom acute leukemia was diagnosed within the first 6 months of life are presented. The four structural chromosomal rearrangements detected in the bone marrow from these patients, i.e., t(7;12)(q36;p13) and t(1;19)(q11;q11) in case 1, t(2;10;11;12)(q21q31;p13;q13;q24) in case 2, and t(11;19)(q23;p13) in case 3, have not previously been associated with congenital leukemia. Acquired chromosomal changes have until now been reported in only 31 leukemic infants in this age group. Of the total material, 18 patients had acute lymphoblastic leukemia and 16 had acute nonlymphocytic leukemia. The by far most frequently recorded cytogenetic aberration has been t(4q;11q), seen in 14 cases of lymphoblastic leukemia. Although t(4q;11q) has not been found in a single patient with acute nonlymphocytic leukemia, these leukemias have often had other rearrangements involving the same region of 11q. Hence, genetic material around 4q21 may be active in lymphocytic differentiation, whereas gene(s) in 11q23 may be important in the neoplastic process in a less cell-type specific manner and perhaps particularly vulnerable to neoplastic rearrangement in fetal life. The finding of four cases out of 34 with translocations between 11q23 and chromosome 19 indicates that this rearrangement might characterize a specific cytogenetic subgroup of leukemia in the very young.
Chromosome analysis of cells from an angioleiomyoma revealed the karyotype 46,XX,del(6)(p21p23),del(21)(q21)/46,XX. The possible importance of these structural derangements is discussed within the framework of current knowledge on chromosome aberrations in benign neoplasms.
Chromosome studies of a solitary plasmocytoma in the femoral bone revealed a near-haploid chromosome number of 31-32 with a loss of one homolog of each chromosome pair except #1, #7, #9, #15, #19-21, and the sex chromosomes (XY). The cytogenetic findings have been compared with 16 cases of near-haploid neoplasms from the literature studied using banding techniques. A common feature present in 13 of the 16 cases reported was found to be disomy 21; the only chromosomes consistently present in one copy in all neoplasms were #2, #3, #4, and #5.
A reciprocal translocation, t(3;12)(q27;q13), was found as the sole karyotypic abnormality in an intramuscular lipoma. The morphology of the derivative 3q+ was strongly reminiscent of the large ring marker we have previously described in three other lipomas, indicating a pathway through which the rings may have arisen. These data, combined with the previous preliminary report by Turc-Carel et al. of a similar t(3;12) in another lipoma strongly suggest that this rearrangement may be a characteristic cytogenetic marker in benign lipogenic tumors.
The cytogenetic, hematologic, and clinical characteristics of a 13-year-old girl with acquired t(6;9)(p23;q34) and dysmyelopoietic syndrome developing into acute myelomonocytic leukemia are described, bringing the total number of patients with t(6;9) and hematologic disease described in the literature up to 19. The diagnosis has been acute myeloid leukemia in the great majority of these patients; only four have had acute myelomonocytic leukemia. High resolution analysis at the 550 band stage localized the breakpoints in chromosomes #6 and #9 to p23 and 9q34.3, respectively. Previous investigations employing high resolution cytogenetics have mapped the typical 9q breakage site in chronic myeloid leukemia to 9q34.1. In situ hybridization studies have demonstrated that the cellular oncogene c-abl remains on the derivative 9q+ chromosome in t(6;9), whereas it is moved to the Ph marker in t(9;22). Thus, the combined data indicate that c-abl is located between 9q34.1 and 9q34.3, i.e., in subband 9q34.2 or its immediate vicinity.
High resolution chromosome analysis was performed on bone marrow cells from four patients with acute promyelocytic leukemia and t(15;17), and in lymphocytes from two unrelated, phenotypically normal persons with an apparently identical constitutional translocation. Scrutiny of prophase-prometaphase chromosomes localized the breakpoints in all six cases to subbands 15q22.3 and 17q11.2. Molecular genetic studies have localized the oncogene c-erbA to chromosome #17 between the breakpoints of the constitutional and the acquired anomaly. The present results, therefore, map c-erbA to subband 17q11.2.
The cytogenetic, clinical, and immunologic findings ina 4-month-old girl with acute lymphoblastic leukemia (ALL) are reported. The malignant lymphoblasts were characterized cytogenetically by the reciprocal translocation t(11;19)(q23;p13); immunologically by an immature pre-B-ALL phenotype. In spite of the high-risk nature of the leukemia, the patient attained complete remission relatively quickly and is still free of disease 3 years after diagnosis. Because the only two previously reported ALL patients with t(11;19) also seem to have responded well to therapy, this cytogenetic abnormality might turn out to be an indicator of favorable prognosis in ALL.
Cytogenetic analysis of a highly malignant osteosarcoma in a 17-year-old girl revealed extremely complex karyotypic changes with several different clonal numerical and structural chromosome aberrations. The composite karyotype was interpreted as 39-41,X,t(X;9)(q11;p24), -1,der(1), -4, -4, -5,i(7q),-8,del(8)(q21),t(10;19)(p13;q13),del(11)(p11p13), t(12;18)(q24;q12), -13,13q+,-14,14p+,-15,15q+,17p+,19q+,-21,+22,+3-6 mar.
The results of the recent European collaborative prenatal study suggested a segregation distortion of balanced pericentric inversions from carrier fathers but not carrier mothers (Boué & Gallano 1984). In an attempt to confirm these unexpected results, we examined 216 pedigrees with balanced pericentric inversions collected from three centers and from the literature. We were unable to detect any significant deviation from the expected 1:1 segregation of balanced pericentric inversions to normal karyotypes among the offspring of either carrier parent. To clarify the discrepancy between the studies, we reanalyzed the data from the prenatal study using all karyotyped individuals and, assuming conventional ascertainment rules, found a normal segregation pattern. We conclude that balanced pericentric inversions segregate normally in both males and females and that some retrospectively selected pedigrees were included as prospective in the prenatal study and this misclassification caused the apparent segregation distortion from carrier fathers.
Thymidine labelling indices (LI) and the number of clonal chromosome aberrations were assessed in fine-needle aspirates from enlarged lymph nodes in 22 patients with non-Hodgkin's lymphoma (NHL). 11 patients had LI greater than 3.0 (median 8.4) and 11 others had LI less than 3.0 (median 1.0). Three categories of chromosome aberration were recorded: normal karyotype, 1-5 aberrations, and greater than or equal to 6 aberrations or multiple complex changes. The distribution of these categories was different among the patients with LI greater than 3.0 compared to those with LI less than 3.0 (p = 0.02). 8 of 11 patients with LI greater than 3.0 had greater than or equal to 6 or complex changes. The corresponding figures for patients with LI less than 3.0 were 2 out of 11. When 16 previously untreated patients were analysed separately, the median number of clonal aberrations was 6.5 in 8 patients with LI greater than 3.0 and 2.5 in 8 others with LI less than 3.0 (p = 0.025). The results suggest that early and spontaneous changes in the genetic material are common in lymphomas with a high proliferative activity. According to previous studies, therapeutic results are especially poor in NHL with high LI. It is proposed that a high proliferative activity of lymphoma cells facilitates an early development of several new mutants and that some of these may be resistant to chemotherapeutic agents.
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Two male siblings (a boy aged 2 years 10 months at death and a male fetus aborted in gestational week 22) showed similar brain and kidney malformations, comprising paraventricular heterotopias, central canal abnormalities (including hydrocephalus in the boy), and glomerular kidney disease with proteinuria. There were no known hereditary diseases in the families of the parents, and there was one healthy sibling of either sex. The malformations thus seem to be hereditary in an autosomal or possibly X linked recessive fashion.