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Karyotypic evolution and tumor progression in head and neck squamous cell carcinomas.

Cytogenetic analysis was performed on primary tumors, and paired recurrent or metastatic lesions, in 14 patients with head and neck squamous cell carcinomas (HNSCC), in order to identify chromosomal aberrations associated with tumor initiation and progression. Abnormal karyotypes were found in 12 of the 14 patients, with distinctive karyotypic similarities shown in all informative pairs. For individual patients, the degree of karyotypic complexity was similar for the primaries and paired recurrent or metastatic lesions. All 22 samples with clonal chromosomal aberrations displayed complex karyotypes with multiple numerical and unbalanced structural rearrangements, resulting in extensive genomic imbalances. The pathway of clonal evolution could be traced in a few patients, supporting the notion that some aberrations or imbalances, particularly partial or entire loss of 3p, i(8q), and homogeneously staining regions commonly mapping to 11q13, were early genetic events in the initiation of HNSCC.

Adult↗

Clonal karyotypic evolution in an embryonal rhabdomyosarcoma with trisomy 8 as the primary chromosomal abnormality.

An embryonal rhabdomyosarcoma was analyzed cytogenetically. In primary cultures fed a serum-containing medium, 11 clones with karyotypic abnormalities were found. One had trisomy 8 only. The other 10 clones had trisomy 8 as well as additional evolutionary changes that included trisomy for part or all of chromosome 2, isochromosomes for the short and long arms of chromosome 11, isochromosomes for the long arm of chromosome 8, and extra copies of chromosome 8, some of which had an interstitial deletion in 8q. In those primary cultures that had grown in a chemically defined, serum-free medium and in all passaged cultures, trisomy 8 was the only aberration. Our findings and a survey of published information point to gain of one chromosome 8 as a frequent primary karyotypic abnormality in embryonal rhabdomyosarcomas. Trisomy for part or all of chromosomes 2 and 11 and additional gains of chromosome 8 material seem to be common secondary changes.

Abdominal Neoplasms↗

Unusual karyotypic evolution in subacute myelomonocytic leukemia in two monozygotic twins.

A subacute myelomonocytic leukemia was diagnosed in 28-month-old cotwins. At this age, their spontaneously dividing cells had a normal karyotype. A few months later, after treatment with 6-mercaptopurine, the following karyotypes were observed: 50,XX, +X, +13, +19, +21 in one and 51,XX, +X, +X, +10, +19, +21 in the other. After bone marrow transplantation, both relapsed although they had received high doses of chemo- and radiotherapy. One developed a clone 46,XX,del(20q), which acquired other clonal rearrangements. The other child developed two different abnormal clones, both with unbalanced rearrangement of chromosome 13. Some of these clones may correspond to immature erythroblasts. The gain of chromosomes, especially for #13, which occurred independently in the cotwins by various mechanisms and at different periods during the disease, is very striking. It may indicate the existence of a strong selective advantage for trisomic 13 cells and may be related to the genetic constitution of the patients.

Bone Marrow Transplantation↗

Karyotypic evolution in a human mucoepidermoid carcinoma.

Chromosomes were studied in cultured material from two different areas of a human mucoepidermoid carcinoma. The detailed banding analyses showed no less than 41 different karyotypes. Comparisons between these revealed (1) that the tumour probably had originated with a normal, diploid stemline; (2) that the progression had mainly proceeded by steps in a hyperdiploid direction, by, as a rule, sequential numerical deviations; and (3) that there existed at least eight further, different, evolutionary products from the original stemline. The complex progressional pattern disclosed in the present case contrasts with cytogenetical data documented for most human benign as well as malignant tumour types.

Aged↗

Genome size, fluorochrome banding, and karyotype evolution in some Hypochoeris species.

Four South American and two European species of Hypochoeris (Asteraceae) were studied using fluorochrome banding, and genome size was determined by flow cytometry, in order to obtain information about microevolution in this genus and about its primary origin. Fluorochrome banding patterns showed GC-rich repeated sequences, particularly around the nucleolar organizer regions. Few differences appeared among the South American species. Nevertheless, determination of nuclear DNA content and base composition revealed significant differences among these species. The phylogenetic position of Hypochoeris robertia, which has the smallest DNA content, is discussed with regard to chromosome evolution in this genus.

Biological Evolution↗

Karyotypic evolution in an originally XY cell line of Drosophila melanogaster: a case of heterochromatin increase in vitro.

The cell line Ca of Drosophila melanogaster, characterized initially by a nearly diploid and normal male karyotype (XY), was used to study chromosomal variation over a period of 5 years of cultivation in vitro. Some general aspects of cell population dynamics which are in accordance with previous findings are pointed out. Various phenomena regarding chromosomal changes leading to karyotype polymorphism are outlined, with a particular emphasis being given to the sex chromosomes. Accordingly, with the aid of fluorescence analysis, some features of the Y and the X chromosomes providing evidence of an enlargement of the heterochromatin (due to addition and to saltatory replication) are described. Moreover, a case of variation in cell morphology accompanied by karyotypic changes was observed, as well as the emergence of a new cell subline of XX type derived from the original of XY type.

Cell Line↗

Karyotype evolution in the bone marrow of a patient with Fanconi anemia: breakpoints in clonal anomalies of this disease.

A 21-year-old Fanconi anemia patient developed refractory anemia. Laboratory studies revealed a transitory increased platelet count and a typical del(5q). Bone marrow karyotyping showed a -6, +der(6)t(1;6)(q12;p25) rearrangement and, two years later, a mosaic -6, +der(6),t(1:6)(q12;p25)/-2, +der 2), t(1;2)(q12;q37) constitution. The chromosome mechanism operating in this patient is discussed.

Adult↗

Clonal karyotypic evolution in a pediatric neurofibrosarcoma.

A retroperitoneal neurofibrosarcoma infiltrating the spine of a 2-year-old boy was investigated cytogenetically three times over a 5-month period. The first sample, from a diagnostic fine-needle aspiration biopsy, had a supernumerary i(1)(q10) as the sole clonal aberration; two cells showed monosomy 18 in addition to the isochromosome. The second sample, obtained at tumor resection 3 weeks later, had the karyotype 47,XY, +i(1)(q10), -18, +21/45,XY, -18. After 5 months, a large local recurrence was resected. The chromosome analysis showed further clonal evolution: 45,XY, +1,der (1;11)dic(1;11)(q44;q13)i(1)(q10), inv(6)(p21q12), -17. The findings indicate that formation of i(1)(q10) and loss of chromosome 18 may be early genetic events in neurofibrosarcoma development.

Child, Preschool↗

The shortest telomeres drive karyotype evolution in transformed cells.

Maintenance of telomeres is essential for chromosome stability. In the absence of telomerase, telomeres shorten with cell division until they approach a stability threshold, at which point cells enter senescence. When senescence-signaling pathways are inactive, further telomere shortening leads to chromosome instability characterized by telomeric fusions and breakage-fusion-bridge (BFB) cycles. Since the distribution of telomere lengths among chromosome extremities is heterogeneous, we wondered about the impact of such variability on the stability of particular chromosome arms. We correlated the initial length of individual telomeres in telomerase-negative-transformed cells with the stability of the corresponding chromosome arms during the precrisis period. We show that arms carrying the shortest telomeres are the first to become unstable and this instability affects the chromosome homologues with shorter telomeres almost exclusively. The analysis of several postcrisis cell populations, which had stabilized their telomeres by re-expressing telomerase, showed that the karyotypic outcome is strongly influenced by the initial telomere length heterogeneity. The timing of telomerase re-expression also seems to play a role in limiting the extent of karyotypic changes, probably by reducing the frequency of telomeric fusions and hence BFB. Since the distribution of telomere lengths within somatic cells is proper to every individual, our results predict that the risk for a particular chromosome arm of becoming unstable early in tumorigenesis will differ between individuals and contribute directly to the heterogeneity of chromosome aberrations found in tumors.

Cell Division↗