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Detection of a t(8;21)(q22;q22) in a case of M5 acute monoblastic leukemia.

Although the translocation (8;21) is the single most common structural rearrangement reported in acute myeloblastic leukemia (AML), it is rarely seen in AML FAB type M5. We describe a case of a 51-year-old male with a diagnosis of acute monoblastic leukemia (AML M5b with hemophagocytic component) whose karyotype showed at (8;21)(q22;22). To our knowledge, this is the first report of this translocation in an AML M5b. The t(8;21) has been associated with a good prognosis, but our patient suffered a fast and fatal evolution.

Chromosomes, Human, Pair 21↗

In situ hybridization (FISH) maps chromosomal homologies between Alouatta belzebul (Platyrrhini, Cebidae) and other primates and reveals extensive interchromosomal rearrangements between howler monkey genomes.

We hybridized whole human chromosome specific probes to metaphases of the black-and-red howler monkey Alouatta belzebul in order to establish chromosomal homology between humans and black-and-red howlers. The results show that the black-and-red howler monkey has a highly rearranged genome and that the human chromosome homologs are often fragmented and translocated. The number of hybridization signals we obtained per haploid set was 40. Nine human chromosome probes gave multiple signals on different howler chromosomes, showing that their synteny is disturbed in A. belzebul. Fourteen black-and-red howler autosomes were completely hybridized by one human autosomal paint, six had two signals, three had three signals, and one chromosome had four signals. Howler chromosomes with multiple signals have produced 12 chromosomal syntenies or hybridization associations which differ from those found in humans: 1/2, 2/20, 3/21, 4/15, 4/16, 5/7, 5/11, 8/18, 9/12, 10/16, 14/15, and 15/22. The hybridization pattern was then compared with those found in two red howler taxa and other mammals. The comparison shows that even within the genus Alouatta numerous interchromosomal rearrangements differentiate each taxa: A. belzebul has six unique apomorphic associations, A. seniculus sara and A. seniculus arctoidea share seven derived associations, and additionally A. seniculus sara has four apomorphic associations and A. seniculus arctoidea seven apomorphic associations. A. belzebul appears to have a more conserved karyotype than the red howlers. Both red and black-and-red howlers are characterized by Y-autosome translocations; the peculiar chromosomal sex system found in the red howler taxa could be considered a further transformation of the A. belzebul sex system. The finding that apparently morphologically similar or even identical taxa have such extreme genomic differences has important implications for speciation theory and neotropical primate conservation.

Alouatta↗

Deletion of 16q11 is a recurrent cytogenetic aberration in acute myeloblastic leukemia during disease progression.

Abnormalities of chromosome 16 other than inv(16)(p13q22), t(16;16)(p13;q22), and del(16)(q22) have not been fully characterized in acute myeloblastic leukemia (AML) and myelodysplastic syndrome (MDS). We report here the first case of AML with del(16)(q11) as a sole abnormality. A 53-year-old woman was initially diagnosed as MDS, refractory anemia with excess of blasts in transformation with normal karyotype. After sixteen months, the disease progressed to overt AML-M1. Myeloblasts were positive for CD13, CD33, and CD34, but negative for HLA-DR. Chromosome analyses of the bone marrow cells showed 46,XX,del(16)(q11) in all metaphase spreads. Multicolor spectral karyotyping also confirmed that del(16)(q11) was not derived from a cryptic translocation, but a simple deletion. Our results, together with three previously reported cases, suggest that del(16)(q11) may be one of the recurrent aberrations in AML and that it could be associated with clonal evolution or disease progression.

Adolescent↗

Rearrangements of chromosome arm 3q in poorly differentiated nasopharyngeal carcinoma.

Cell lines were established from fresh tumor biopsies from two Saudi patients with poorly differentiated nasopharyngeal carcinoma (NPC). Cytogenetic analysis on Giemsa-banded metaphase cells revealed complex, abnormal karyotypes in both patients with modal chromosome numbers of 77 and 52. A der(3)dup(3)(q25-q2?7) or t(3;?)(q27;?) was observed in both cell lines. The rearrangements involving chromosomes X, 1, 4, 6, 7, 8, 12, 13, 15, 17, and 22 in the first patient and 1, 6, and 22 in the second patient could represent clonal evolution.

Adult↗

[Intraspecies phylogenetic connections in Sorex araneus L.: a southern Baltic subgroup of chromosome races].

Results of chromosome G-banding were used to identify two new karyotypic races of the common shrew (Sorex araneus L.) in the European part of Russia. The chromosomal diagnosis of race St. Petersburg included five metacentrics (hk, ip, jl, mq, and nr) and two acrocentrics (g and o) (2Na = 20); the diagnosis of race West Dvina included six metacentrics (gm, hk, ip, jl, no, and qr) (2Na = 18). The phylogenetic significance of the chromosomal markers gm, hk, and ip is considered and the possibility of reticulate evolution in the species S. araneus is discussed.

Animals↗

Cytogenetic and morphological abnormalities in paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by the expansion of a haematopoietic stem cell clone with a PIG-A mutation (the PNH clone) in an environment in which normal stem cells are lost or failing: it has been hypothesized that this abnormal marrow environment provides a relative advantage to the PNH clone. In patients with PNH, generally, the karyotype of bone marrow cells has been reported to be normal, unlike in myelodysplastic syndrome (MDS), another clonal condition in which cytogenetic abnormalities are regarded as diagnostic. In a retrospective review of 46 patients with a PNH clone, we found a karyotypic abnormality in 11 (24%). Upon follow-up, the proportion of cells with abnormal karyotype decreased significantly in seven of these 11 patients. Abnormal morphological bone marrow features reminiscent of MDS were common in PNH, regardless of the karyotype. However, none of our patients developed excess blasts or leukaemia. We conclude that in patients with PNH cytogenetically abnormal clones are not necessarily malignant and may not be predictive of evolution to leukaemia.

Adolescent↗

Comparative high-resolution mapping of human and primate chromosomes by fluorescence in situ hybridization.

A molecular cytogenetic approach that facilitates high-resolution comparative mapping of defined human genes in different primate species is presented. Fluorescence in situ hybridization and digital imaging microscopy were used to visualize human DNA probes on simultaneously banded or "painted" metaphase chromosomes of great apes (Pan troglodytes, Gorilla gorilla, Pongo pygmaeus), hylobatids (Hylobates lar and Hylobates syndactylus), and Old World monkeys (Macaca fuscata and Cercopithecus aethiops). Using a series of DNA probes, chromosomal rearrangements in the karyotypes of primates were readily detected at the molecular cytogenetic level. This approach should contribute considerably to the understanding of primate phylogeny and evolution.

Animals↗

Compound kinetochores of the Indian muntjac. Evolution by linear fusion of unit kinetochores.

The chromosomes of the Indian muntjac (Muntiacus muntjak vaginalis) are unique among mammals due to their low diploid number (2N = 6 female, 7 male) and large size. It has been proposed that the karyotype of this small Asiatic deer evolved from a related deer the Chinese muntjac (Muntiacus reevesi) with a diploid chromosome number of 2n = 46 consisting of small telocentric chromosomes. In this study we utilized a kinetochore-specific antiserum derived from human patients with the autoimmune disease scleroderma CREST as an immunofluorescent probe to examine kinetochores of the two muntjac species. Since CREST antiserum binds to kinetochores of mitotic chromosomes as well as prekinetochores in interphase nuclei, it was possible to identify and compare kinetochore morphology throughout the cell cycle. Our observations indicated that the kinetochores of the Indian muntjac are composed of a linear beadlike array of smaller subunits that become revealed during interphase. The kinetochores of the Chinese muntjac consisted of minute fluorescent dots located at the tips of the 46 telocentric chromosomes. During interphase, however, the kinetochores of the Chinese muntjac clustered into small aggregates reminiscent of the beadlike arrays seen in the Indian muntjac. Morphometric measurements of fluorescence indicated an equivalent amount of stained material in the two species. Our observations indicate that the kinetochores of the Indian muntjac are compound structures composed of linear arrays of smaller units the size of the individual kinetochores seen on metaphase chromosomes of the Chinese muntjac. Our study supports the notion that the kinetochores of the Indian muntjac evolved by linear fusion of unit kinetochores of the Chinese muntjac. Moreover, it is concluded that the evolution of compound kinetochores may have been facilitated by the non-random aggregation of interphase kinetochores in the nuclei of the ancestral species.

Animals↗

Fluorescence in situ hybridization improves cytogenetic results in the analysis of hepatoblastoma.

Hepatoblastoma (HB) is the most frequent malignant liver tumor in children. Cytogenetic data indicate the presence of recurring trisomies of the chromosomes 2, 8, and 20, but more work is needed to clarify their incidence and prognostic significance. Cytogenetic analysis is limited by the requirement of suitable cells in metaphase. A different method that increases analysis sensitivity is fluorescence in situ hybridization (FISH). We studied 20 cases of hepatoblastoma; FISH analysis obtained results in 10 cases of HB with no informative karyotype. In 5 of 10 of these cases at least one trisomic clone was detected, which always coexisted with a population of diploid cells. These results confirm that trisomy 20 and/or 2 and 8 coexisting with diploid cells is a frequent finding in hepatoblastoma and provide further support to the clonal evolution theory: indeed, trisomy 20 was the most frequently detected abnormality, followed by trisomy of chromosomes 2 and 8. In view of the high incidence of recurrent trisomies, FISH analysis should be recommended in all the cases of HB with no informative karyotype.

Adult↗

Chromosome study of 85 patients with myelodysplastic syndrome.

We studied bone marrow chromosomes in 85 consecutive patients with myelodysplastic syndrome (MDS). Fifty-seven (67%) had a clone with an abnormal karyotype at diagnosis. Eight had secondary MDS, all with abnormal karyotypes. The frequency of abnormal karyotypes in the primary MDS was 64.9%. During subsequent follow-up, five patients acquired chromosome abnormalities; thus, at the end of the study, 72.0% of patients had an abnormal karyotype. The most frequent chromosome abnormalities were 5q-, +8, -7, -5, and -22. Forty patients (i.e., 70% of those with an abnormal karyotype and 47% of the whole group) had one of the karyotype abnormalities associated with secondary MDS or acute nonlymphocytic leukemia; in other words, 5q- or -5, or -7. Of all patients, 21.1% progressed into ANLL. Unfavorable prognostic factors associated with the risk of evolution into ANLL and with shorter overall survival were the presence of greater than 5% of bone marrow blasts, major chromosome abnormalities, and monosomy 7.

Acute Disease↗

A heterochromatic satellite DNA is highly amplified in a single chromosome of Muscari (Hyacinthaceae).

We examined the composition and evolution of a large heterochromatic region present in the genomes of certain species of the genus Muscari (Hyacinthaceae). We found that in Muscari comosum this heterochromatic region is composed mainly of a satellite DNA family, which we named MCSAT. Molecular analyses and in situ hybridization revealed that, through the evolution of Muscari species, the MCSAT sequences have been progressively amplified in several species of the genus, such as M. matritensis and M. dionysicum, attaining enormous amplification in the genome of M. comosum. We discuss the characteristics of this satellite DNA family, which, being exclusively amplified in one chromosome pair of M. comosum, constitute the major exception to the equilocal model of satellite DNA and heterochromatin distribution. Also, we discuss the possibility that the amplification of these sequences in a single chromosome could have contributed to a progressive increase in the asymmetry of the karyotypes in Muscari species.

Base Sequence↗

Chromosomal segregation and fertility in Robertsonian chromosomal heterozygotes of the house musk shrew (Suncus murinus, Insectivora, Soricidae).

Crucial to our understanding of chromosomal variation and evolution in mammals are detailed studies of chromosomal heterozygotes, with analyses of chromosomal segregation and chromosome-derived infertility. We studied segregation and fertility in hybrids between karyotypic races of the house musk shrew Suncus murinus. These individuals were heterozygous for up to five Robertsonian fusions (Rbs) and an insertion of heterochromatin in an autosome. All variant chromosomes showed Mendelian segregation and all Rbs segregated independently of each other in the progeny of double heterozygotes. Litter size in single and even multiple Rb heterozygotes was no smaller than that in the less fertile parental strain. The effects of genetic background were more important in determining litter size than Rb heterozygosity for the shrews that we examined.

Animals↗

Clonal drift and role of chromosome dosage in human melanoma metastatic cell lines: a statistical analysis.

Karyotypic analyses were performed on twenty human melanoma clones and variants all deriving, following in vivo selections and/or in vitro cloning, from the parental M4Be cell line, but expressing different tumorigenicity (expressed as mean tumor weight) and metastatic ability (expressed as pulmonary metastasis frequency) after s.c. injection in antithymocyte immunosuppressed newborn rats. These cells were hypertriploid, showing quite comparable modal numbers (around 70). They all expressed a wide range of chromosome number per mitosis (28 to 198), as well as a large extent of karyotypic heterogeneity, showed by extensive clonal drifts within the different cell lines. Their common origin was ascertained by five clonal abnormal marker chromosomes deriving from chromosomes 6, 7, 8, 9, 11 and 14. Twenty-one additional marker chromosomes, most of them non clonal, were observed in the different cell lines. We developed a statistical analysis to search for putative relationship between the expression of tumorigenicity and metastatic ability and the evolution of specific subclones within the different cell lines. We showed that the expression of a high mean tumor weight and/or a high metastasis incidence was related to the modification of the ratio of different subclones within each cell line, and more especially to the emergence of subclones presenting partial losses of individual chromosomes or chromosomal fragments, which were encountered with a lower frequency in the low metastatic cell lines. The biological relevance of these findings in terms of clonal evolution and role of chromosome dosage in tumor progression is discussed.

Chromosome Aberrations↗

Female mating behaviour, sexual selection and chromosome I inversion karyotype in the seaweed fly, coelopa frigida

Previous studies of the seaweed fly, Coelopa frigida, have revealed the operation of several different forces of sexual selection. The overall pattern of mate choice seen in natural populations is not consistent with the predictions of indirect sexual selection as females do not express preferences that maximize the fitness of their offspring, even though the benefits from such choice are relatively large in this species. Thus, the maintenance of female mate choice for large male size must instead either be a result of a direct benefit to the female of mating with large males, or a side-effect of the evolution of another character, in other words pleiotropy. In order to separate these two alternatives the genetical basis of female mating behaviour needs to be studied. Previous studies have revealed associations between chromosomal inversion karyotype and both general female willingness to mate and mate choice for large male size, however these associations were lost after several generations of laboratory culture. Here several isokaryotypic lines from wild collections of flies were derived. The willingness to mate and mate choice of females from each line were determined. Pairs of lines of opposite inversion karyotype that significantly differed in either or both willingness to mate and mate choice were crossed. The mating behaviour and inversion karyotype of the F2 progeny (all F1 progeny are heterokaryotypes) were determined. Clear differences in the general levels of female willingness to mate were found between the two inversion homokaryotypes in several families, whereas variation in the strength of female choice for large male size were not revealed. It is suggested that mate choice in this species occurs as a pleiotropic effect of selection acting on female willingness to mate.

Journal Article↗

Losses of 1p and chromosome 14 in renal oncocytomas.

We performed cytogenetic analyses of 8 renal oncocytomas to identify chromosomal regions involved in the tumorigenesis of oncocytomas. All cases showed chromosomal findings corresponding to established cytogenetic subsets of renal oncocytomas: 3 cases with normal karyotypes, 1 case with rearrangement of 11q, and 4 cases with losses of chromosome 14. In the latter cytogenetic subgroup, monosomy 14 was additionally accompanied by either monosomy 1 in 2 cases or loss of 1p in a third case, providing insights in the cytogenetic evolution of this subgroup.

Adenoma, Oxyphilic↗

Spontaneous clinical and cytogenetic remission of aplastic anemia in a patient with del(13q).

We describe the case of a 64-year-old Japanese man with pancytopenia. Bone marrow biopsy findings were consistent with aplastic anemia. The patient was treated by transfusions without immunosuppressive therapy. Chromosome analysis of bone marrow cells at 6 months after onset showed a 46,XY,del(13) (q14q22) karyotype. The pancytopenia resolved gradually over the next 5 years; chromosome analysis of bone marrow cells at that time yielded normal findings. To our knowledge, this is the first report of spontaneous hematologic and cytogenetic remission of aplastic anemia. These findings suggest that the abnormal clone with deletion of the long arm of chromosome 13 was not sufficient for clonal evolution in aplastic anemia in this case.

Anemia, Aplastic↗

A genealogical view of chromosomal evolution and species delimitation in the Drosophila virilis species subgroup.

Chromosomal arrangement was a historically important character used for defining taxonomic boundaries. The Drosophila virilis species group exhibits a series of chromosomal rearrangements, and the resulting differences among karyotypes were primary characters originally used to define taxa within the group. However, some chromosomally divergent forms have not been sufficiently resolved in phylogenetic reconstructions of DNA sequences from several nuclear genes. Sequences of mitochondrial regions have the potential for finer-scale resolution of closely related taxa; therefore, sequences of two mitochondrial genes were used to examine phylogenetic relationships within the chromosomally variable virilis subgroup. Sequences were obtained from multiple strains of the Palearctic species, D. virilis and D. lummei, and the Nearctic species, D. novamexicana and two chromosomal forms of D. americana. Analyses support the recent emergence of the different chromosomal forms in North America. However, none of these chromosomally divergent forms exhibit reciprocal monophyly of their mtDNA sequences, which is the requirement for attaining genealogical species status.

Animals↗