1.
Mertens, Fredrik, et al.
(författare)
Radiation-associated sarcomas are characterized by complex karyotypes with frequent rearrangements of chromosome arm 3p
2000
Ingår i: Cancer Genetics and Cytogenetics. - 0165-4608. ; 116:2, s. 89-96
Tidskriftsartikel (refereegranskat) abstract
Ionizing radiation is a well-known risk factor for sarcoma development. To investigate whether radiation-associated sarcomas are characterized by chromosome aberrations that distinguish them from de novo sarcomas, we identified those patients in our series of more than 500 cytogenetically abnormal sarcomas that fulfilled the following criteria: (1) each patient should have been irradiated for another malignancy at least 3 years prior to the sarcoma diagnosis, and (2) the sarcoma should have developed within the field of radiation. Ten patients fulfilling these criteria could be retrieved (median age at sarcoma diagnosis was 55 years, range 17-79; median latency period between primary tumor and radiation-associated sarcoma was 9 years, range 4-30). The diagnoses were typical for radiation-associated sarcomas: 2 each of malignant fibrous histiocytoma, leiomyosarcoma, and pleomorphic sarcoma, and 1 each of osteosarcoma, fibrosarcoma, myxofibrosarcoma, and spindle cell sarcoma. All 10 cases had relatively complex karyotypes with multiple, mostly unbalanced, structural rearrangements, similar to what has been reported in de novo sarcomas of the corresponding histologic subtypes. The only cytogenetic features that were unusually frequent among the radiation-associated sarcomas were the finding of unrelated clones in 3 cases, and loss of material from chromosome arm 3p, in particular 3p21-3pter, in 8 cases. Loss of the same chromosome segment has been described in 4 of the 8 previously published cases of radiation-associated sarcomas that have been analyzed after short-term culturing, which makes this imbalance significantly (P < 0.001) more frequent among radiation-associated sarcomas (12 of 18 cases) than among unselected cases of the corresponding histologic subtypes (74 of 282 cases). In contrast to the cytogenetic results, no 3p deletions were detected among the 6 cases of the present series that could be analyzed by comparative genomic hybridization (CGH). The most frequent imbalance detected by CGH was gain of 15cen-q15 (3 cases), followed by loss of chromosome 13 and gain of 5p, and 7cen-q22, each detected in 2 cases.
2.
Johansson, Bertil, et al.
(författare)
Granulocytic sarcomas in body cavities in childhood acute myeloid leukemias with 11q23/MLL rearrangements
2000
Ingår i: Genes, Chromosomes and Cancer. - 1045-2257. ; 27:2, s. 136-142
Tidskriftsartikel (refereegranskat) abstract
Three childhood acute monoblastic leukemias (AML M5) with granulocytic sarcomas (GSs) are described. All displayed 11q23/MLL abnormalities, t(9;11)(p22;q23) in two cases and t(11;17)(q23;q21) in one case, constituting around 20% of all 11q23-positive AML cytogenetically investigated in our department. Two of the patients had GS in multiple locations, and all three had abdominal GS. In two of them, t(9;11)-positive GS was diagnosed prior to the diagnosis of AML. Fourteen (1.9%) of 752 published AML cases with 11q23 aberrations have had GS, either as a presenting feature or during disease progression. The incidence of GS has varied significantly (P < 0.05) between children (3.8%) and adults (0.8%). The most common AML subtype has been AML M5 ( approximately 75%) and the most frequent GS sites have been the skin, abdomen, orbit, and thorax. Considering the possibility of underreporting of GS in published cases and the relatively high frequency in our own series, we believe that 11q23/MLL rearrangements may predispose to GS development. Although extramedullary infiltrates in the skin are known to be frequent in cases of AML M5, which is often associated with 11q23 aberrations, the present findings indicate that GS in the abdomen, orbit, and thorax may also be common, especially in pediatric AML. Thus, the possibility of 11q23/MLL-positive GS should be suspected when tumors of uncertain derivation occur in these sites. Finally, the identification of 11q23/MLL abnormalities in GSs in two patients without overt AML underscores the importance of using cytogenetic and molecular genetic investigations as a diagnostic approach in the evaluation of tumorous lesions of unknown origin.
3.
Mauritzson, Nils, et al.
(författare)
Survival time in a population-based consecutive series of adult acute myeloid leukemia--the prognostic impact of karyotype during the time period 1976-1993
2000
Ingår i: Leukemia. - 1476-5551. ; 14:6, s. 1039-1043
Tidskriftsartikel (refereegranskat) abstract
A consecutive population-based series of 372 adult acute myeloid leukemias, successfully cytogenetically investigated at a single center between 1976 and 1993, is reported. All medical records were reviewed in order to ascertain the prognostic impact of karyotype, divided into three groups; favorable (t(8;21), t(15;17), and inv(16) irrespective of karyotypic complexity; n = 40), poor (der(1;7), inv(3), -5, del(5q), -7, t(9;22), and complex karyotypes including whole or partial losses of chromosomes 5 and/or 7; n = 56), and intermediate (other abnormalities or normal karyotype; n = 276). The possible modification by age, gender, time period, morphologic subtype, and bone marrow transplantation (BMT) on this prognostic impact was also determined. The chemotherapy regimens used were heterogeneous over time but principally the same at any given point in time. The majority of the patients were treated with combinations including an anthracycline and cytarabine with curative intent. Gender, morphology, and BMT did not significantly modify the effect of cytogenetic patterns on survival time, whereas age and time period did. The hazard ratios for the subgroups favorable, intermediate, and poor were 1.0, 1.2 and 1.9 at age 20-49; 1.0, 2.5 and 4.5 at age 50-64; 1.0, 4.1 and 11.4 at age 65-74; 1.0, 1.4 and 2.2 for the time period 1976-1987 and 1.0, 2.0 and 6.7 for 1988-1993. The salient feature of the Kaplan-Meier curves was the improved survival during the later time period for patients with favorable and intermediate cytogenetic abnormalities. The present findings thus suggest that it is mainly these patient groups that have benefited from advances in therapy, including supportive care.
