Taxonomical and biogeographical problems in Mediterranean shrews of the genus Crocidura (Mammalia, Insectivora) with reference to a new karyotype from Sicily (Italy)

Shrews of the genus Crocidura from Sicily revealed a new karyotype from Europe: 2n = 36, NF = 56, NFa = 52. With reference to the revision of Vesmanis (1976), this shrew is provisionally attributed to C. caudata Miller, 1901 and it is proposed to call it the "Sicilian shrew". Its chromosome complement is similar to that of shrews from Canary Islands and a species from Burundi (Central Africa), suggesting that it might have split off from a line of Paleotropical origin. Following these findings, the modern concept of Mediterranean island colonization by shrews must be revised. The distinctive characteristics of Mediterranean shrews should also be revised.

The amphioxus genome and the evolution of the chordate karyotype.

Lancelets ('amphioxus') are the modern survivors of an ancient chordate lineage, with a fossil record dating back to the Cambrian period. Here we describe the structure and gene content of the highly polymorphic approximately 520-megabase genome of the Florida lancelet Branchiostoma floridae, and analyse it in the context of chordate evolution. Whole-genome comparisons illuminate the murky relationships among the three chordate groups (tunicates, lancelets and vertebrates), and allow not only reconstruction of the gene complement of the last common chordate ancestor but also partial reconstruction of its genomic organization, as well as a description of two genome-wide duplications and subsequent reorganizations in the vertebrate lineage. These genome-scale events shaped the vertebrate genome and provided additional genetic variation for exploitation during vertebrate evolution.

Habitat, morphology and karyotype of the Saharan shrew Crocidura tarfayaensis (Mammalia : Soricidae)

The Saharan shrew Crocidura tarfayaensis Vesmanis and Vesmanis, 1980, has a limited disribution along the Atlantic coast of Sahara, south of Agadir (Morocco) through Western Sahara into Mauritania and is only known from few captures and some owl pellets. Here we report field data from the successful trapping of five specimens of C. tarfayaensis in the Guelmim region. The habitat was characterized by sand dunes along a river, with dense shrubberies of Tamarix sp., the huge grass Erianthus ravennae (Poaceae) and flat bushes of Atriplex glauca var. ifniensis (Chenopodiaceae). Morphological discrimination with C. whitakeri were examined. The chromosomes of C. tarfayaensis revealed a karyotype of 2n = 36, similar to that of the Canary shrew C. canariensis and the Sicilian shrew C. sicula. In conclusion, C. tarfayaensis seems to be a descendant of the presumed continental ancestor of the two island species.

Impact of Balanced or Unbalanced Karyotype At Diagnosis On Prognosis of CML: Long-Term Observation From 1346 Patients of the Randomized CML Study IV

Introduction: Acquired genetic instability in chronic myeloid leukemia (CML) as a consequence of the translocation t(9;22)(q34;q11) and the resulting BCR-ABL fusion causes the continuous acquisition of additional chromosomal aberrations and mutations and thereby progression to accelerated phase (AP) and blast crisis (BC). At least 10% of patients in chronic phase (CP) CML show additional alterations at diagnosis. This proportion rises during the course of the disease up to 80% in BC. Acquisition of chromosomal changes during treatment is considered as a poor prognostic indicator, whereas the impact of chromosomal aberrations at diagnosis depends on their type. Patients with major route additional chromosomal alterations (major ACA: +8, i(17)(q10), +19, +der(22)t(9;22)(q34;q11) have a worse outcome whereas patients with minor route ACA show no difference in overall survival (OS) and progression-free survival (PFS) compared to patients with the standard translocation, a variant translocation or the loss of the Y chromosome (Fabarius et al., Blood 2011). However, the impact of balanced vs. unbalanced (gains or losses of chromosomes or chromosomal material) karyotypes at diagnosis on prognosis of CML is not clear yet. Patients and methods: Clinical and cytogenetic data of 1346 evaluable out of 1544 patients with Philadelphia and BCR-ABL positive CP CML randomized until December 2011 to the German CML-Study IV, a randomized 5-arm trial to optimize imatinib therapy by combination, or dose escalation and stem cell transplantation were investigated. There were 540 females (40%) and 806 males (60%). Median age was 53 years (range, 16-88). The impact of additional cytogenetic aberrations in combination with an unbalanced or balanced karyotype at diagnosis on time to complete cytogenetic and major molecular remission (CCR, MMR), PFS and OS was investigated. Results: At diagnosis 1174/1346 patients (87%) had the standard t(9;22)(q34;q11) only and 75 patients (6%) had a variant t(v;22). In 64 of 75 patients with t(v;22), only one further chromosome was involved in the translocation; In 8 patients two, in 2 patients three, and in one patient four further chromosomes were involved. Ninety seven patients (7%) had additional cytogenetic aberrations. Of these, 44 patients (3%) lacked the Y chromosome (-Y) and 53 patients (4%) had major or minor ACA. Thirty six of the 53 patients (2.7%) had an unbalanced karyotype (including all patients with major route ACA and patients with other unbalanced alterations like -X, del(1)(q21), del(5)(q11q14), +10, t(15;17)(p10;p10), -21), and 17 (1.3%) a balanced karyotype with reciprocal translocations [e.g. t(1;21); t(2;16); t(3;12); t(4;6); t(5;8); t(15;20)]. After a median observation time of 5.6 years for patients with t(9;22), t(v;22), -Y, balanced and unbalanced karyotype with ACA median times to CCR were 1.05, 1.05, 1.03, 2.58 and 1.51 years, to MMR 1.31, 1.51, 1.65, 2.97 and 2.07 years. Time to CCR and MMR was longer in patients with balanced karyotypes (data statistically not significant). 5-year PFS was 89%, 78%, 87%, 94% and 69% and 5-year OS 91%, 87%, 89%, 100% and 73%, respectively. In CML patients with unbalanced karyotype PFS (p<0.001) and OS (p<0.001) were shorter than in patients with standard translocation (or balanced karyotype; p<0.04 and p<0.07, respectively). Conclusion: We conclude that the prognostic impact of additional cytogenetic alterations at diagnosis of CML is heterogeneous and consideration of their types may be important. Not only patients with major route ACA at diagnosis of CML but also patients with unbalanced karyotypes identify a group of patients with shorter PFS and OS as compared to all other patients. Therefore, different therapeutic options such as intensive therapy with the most potent tyrosine kinase inhibitors or stem cell transplantation are required.

Importance clinique du caryotype en hématologie. [Clinical importance of karyotype in hematology.]

Cytogenic analysis of leukemic cells has proven to be a mandatory part of the diagnosis of malignant hemopathies. Recurring clonal cytogenetic abnormalities may be divided into those exclusively associated with myeloid disorders, those uniquely observed in lymphoid diseases, and those detected in both myeloid and lymphoid hemopathies. Several of the common defects are characteristic of specific FAB types or subtypes and are associated with specific clinico pathologic syndromes and clinical complications. Cytogenetic abnormalities have served to define relatively homogeneous subsets of malignant hemopathies which are not evident from morphological and other available markers. Cytogenetic findings have been demonstrated to be powerful indicators in predicting clinical course and outcome in patients and in guiding their management. Given the significant progress made in the treatment of malignant hemopathies, it is very important to identify parameters which may be used to predict whether patients will respond favorably to standard therapies or if they are unlikely to do so and require alternative strategies, such as bone marrow transplantation. Cytogenetic studies have also provided important insights into the understanding of malignant transformation processes. In a number of recurring chromosome translocations characteristic of leukemias and lymphomas the genes that are located at the breakpoints have been identified. Molecular analysis has revealed that alteration in expression of these genes or in the properties of the encoded proteins resulting from the rearrangements plays an integral part in malignant transformation. Studies of clonality have suggested that several chromosome abnormalities may arise in pluripotent hemopoietic stem cells, whereas others may originate in cells of more restricted lineage. The author focuses first on the implications of the karyotype in the diagnosis and the prognosis of myeloproliferative syndromes, acute leukemias and myelodysplastic syndromes, then on the interest of describing new clinical-cytogenetic associations. Finally, some of the recent results obtained in a cytogenetic study of myelodysplastic syndromes are discussed.

The karyotype of Crocidura flavescens (Mammalia, Insectivora) in South Africa

Karyological results give evidence that the South African Crocidura flavescens (Geoffroy, 1827) is not conspecific with the West and East African giant shrews of the taxa spurrelli, manni, kivu and olivieri

Crocidura cossyrensis Contoli, 1989 (Mammalia, Soridiae): karyotype, biochemical genetics and hybridization experiments

Crocidura cossyrensis Contoli, 1989 (Mammalia, Soricidae): karyotype, biochemical genetics and hybridization experiments. - The shrew Crocidura cossyrensis Contoli, 1989 from Pantelleria (I), a Mediterranean island 100 km south of Sicily and 70 km west from Tunisia, was investigated in order to understand its origin and its relationship with C. russula from Tunisia, Morocco and Switzerland. With the exception of a single heterozygote centric fusion, C. cossyrensis had a karyotype identical with that of C russula from Tunisia (2N = 42, NF = 70 to 72), but it differed from C russula from Morocco and Switzerland (2N = 42, NF = 60). The former have 5-6 pairs of chromosomes with small arms that are acrocentric in the latter. Genetic comparisons with allozyme data revealed small genetic distance (0.04) between C cossyrensis and C russula from Tunisia. In contrast, this eastern clade (Tunisia and Pantelleria) is separated from the western clade (Switzerland and Morocco) by a genetic distance of 0.14. A hybridization experiment between shrews from Pantelleria and Switzerland lead rapidly to an F1 generation. From 12 F1 hybrids that were backcrossed, females reproduced normally, but none of the males did so. Concluding from the results, C. cossyrensis from Pantelleria and C. russula cf. agilis from Tunisia belong to the same taxon that may have reached the differentiation of a biological species within the C. russula group. More geographic samples are needed to determine the definitive taxonomic positions of these shrews.

Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype.

PURPOSE: To investigate the prognostic value of various cytogenetic components of a complex karyotype in acute myeloid leukemia (AML). PATIENTS AND METHODS: Cytogenetics and overall survival (OS) were analyzed in 1,975 AML patients age 15 to 60 years. RESULTS: Besides AML with normal cytogenetics (CN) and core binding factor (CBF) abnormalities, we distinguished 733 patients with cytogenetic abnormalities. Among the latter subgroup, loss of a single chromosome (n = 109) conferred negative prognostic impact (4-year OS, 12%; poor outcome). Loss of chromosome 7 was most common, but outcome of AML patients with single monosomy -7 (n = 63; 4-year OS, 13%) and other single autosomal monosomies (n = 46; 4-year OS, 12%) did not differ. Structural chromosomal abnormalities influenced prognosis only in association with a single autosomal monosomy (4-year OS, 4% for very poor v 24% for poor). We derived a monosomal karyotype (MK) as a predictor for very poor prognosis of AML that refers to two or more distinct autosomal chromosome monosomies (n = 116; 4-year OS, 3%) or one single autosomal monosomy in the presence of structural abnormalities (n = 68; 4-year OS, 4%). In direct comparisons, MK provides significantly better prognostic prediction than the traditionally defined complex karyotype, which considers any three or more or five or more clonal cytogenetic abnormalities, and also than various individual specific cytogenetic abnormalities (eg, del[5q], inv[3]/t[3;3]) associated with very poor outcome. CONCLUSION: MK enables (in addition to CN and CBF) the prognostic classification of two new aggregates of cytogenetically abnormal AML, the unfavorable risk MK-negative category (4-year OS, 26% +/- 2%) and the highly unfavorable risk MK-positive category (4-year OS, 4% +/- 1%).

G-banded karyotype of the alpine shrew, Sorex alpinus (Mammalia, Soricidae), from the Sumava Mts

The G-banded karyotype of two individuals of the alpine shrew Sorer alpinus collected from the Sumava Mountains (Czech Republic) is presented. The diploid number of chromosomes was 56 and both the morphology and the G-banding pattern of chromosomes appeared to be very similar Gto those reported from the Alps and the Jura Mountains. This is the first report on the G-banded chromosomes of this species outside Switzerland and eastern France.

Repeated Whole-Genome Duplication, Karyotype Reshuffling, and Biased Retention of Stress-Responding Genes in Buckler Mustard.

Whole-genome duplication (WGD) is usually followed by gene loss and karyotype repatterning. Despite evidence of new adaptive traits associated with WGD, the underpinnings and evolutionary significance of such genome fractionation remain elusive. Here, we use Buckler mustard (Biscutella laevigata) to infer processes that have driven the retention of duplicated genes after recurrent WGDs. In addition to the β- and α-WGD events shared by all Brassicaceae, cytogenetic and transcriptome analyses revealed two younger WGD events that occurred at times of environmental changes in the clade of Buckler mustard (Biscutelleae): a mesopolyploidy event from the late Miocene that was followed by considerable karyotype reshuffling and chromosome number reduction and a neopolyploidy event during the Pleistocene. Although a considerable number of the older duplicates presented signatures of retention under positive selection, the majority of retained duplicates arising from the younger mesopolyploidy WGD event matched predictions of the gene balance hypothesis and showed evidence of strong purifying selection as well as enrichment in gene categories responding to abiotic stressors. Retention of large stretches of chromosomes for both genomic copies supported the hypothesis that cycles of WGD and biased fractionation shaped the genome of this stress-tolerant polypolyloid, promoting the adaptive recruitment of stress-responding genes in the face of environmental challenges.

New Sorex araneus karyotypes from Germany and the postglacial recolonization of central Europe

New G-banded karyotypes from populations of the common shrew Sorex araneus Linnaeus, 1758 provide a clearer picture of the distribution of chromosome races in central Europe. As expected according to their occurrence in neighbouring countries, the Jutland (kq, no), Laska (k/o) and Drnholec (ko, nr) races are also found in Germany. A new chromosome race "Rugen" (kq) is described from this Baltic Island. Together with the previously recorded races Ulm and Mooswald (kr), six chromosome races are now known from Germany. The resulting distribution pattern is characterized by high frequencies of different race-specific metacentrics at the periphery of the country and clines with decreasing frequencies towards the centre which is occupied by the Ulm race. This race is acrocentric for all chromosome arms involved in the observed race-specific fusions and represents a buffer between the surrounding, more metacentric races. According to the present distribution of these metacentrics, a scenario for the postglacial recolonization of central Europe by S. araneus populations on three different routes is proposed: from the east along the northern slopes of the Carpathian Arc, from the south-east along the Danube Valley and from the south-west through the Upper Rhine Valley.

Soft tissue sarcomas with complex genomic profiles.

Soft tissue sarcomas (STS) with complex genomic profiles (50% of all STS) are predominantly composed of spindle cell/pleomorphic sarcomas, including leiomyosarcoma, myxofibrosarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma, malignant peripheral nerve sheath tumor, angiosarcoma, extraskeletal osteosarcoma, and spindle cell/pleomorphic unclassified sarcoma (previously called spindle cell/pleomorphic malignant fibrous histiocytoma). These neoplasms show, characteristically, gains and losses of numerous chromosomes or chromosome regions, as well as amplifications. Many of them share recurrent aberrations (e.g., gain of 5p13-p15) that seem to play a significant role in tumor progression and/or metastatic dissemination. In this paper, we review the cytogenetic, molecular genetic, and clinicopathologic characteristics of the most common STS displaying complex genomic profiles. Features of diagnostic or prognostic relevance will be discussed when needed.

99mTc-sestamibi imaging and bone marrow karyotyping in the assessment of multiple myeloma and MGUS

AIM: The first pathogenetic step in multiple myeloma is the emergence of a limited number of clonal plasma cells, clinically known as monoclonal gammopathy of undetermined significance (MGUS). Patients with MGUS do not have symptoms or end-organ damage but they do have a 1% annual risk of progression to multiple myeloma or related malignant disorders. With progression of MGUS to multiple myeloma, complex genetic events occur in the neoplastic plasma cell. Karyotyping and fluorescence in-situ hybridization (FISH) were shown to be of prognostic value in patients with multiple myeloma. Tc-sestamibi imaging reflects myeloma disease activity in bone marrow with very high sensitivity and specificity predicting disease evolution. This study was undertaken to evaluate the role of Tc-sestamibi imaging and cytogenetic analysis in prognosis prediction of MGUS and multiple myeloma. METHODS: We enrolled 30 consecutive patients with a confirmed diagnosis of multiple myeloma or MGUS. Bone marrow biopsy and biochemical staging according to the International Staging System (ISS) were performed in all cases. Karyotype analysis and FISH were performed in 11 of 12 patients with MGUS and in 17 of 18 patients with multiple myeloma having adequate metaphases. RESULTS: The karyotype was abnormal in four of 11 MGUS and in six of 17 multiple myeloma. Abnormalities of chromosome 13 were present in one case of MGUS and in six cases of multiple myeloma whereas the involvement of immunoglobulin was observed in one case of multiple myeloma. An abnormal FISH panel was found in four MGUS and nine multiple myeloma patients. All patients with MGUS showed a normal MIBI scan (score 0). Among patients with multiple myeloma only three, all with ISS stage I, showed a normal scan while a positive scan was obtained in others (score range, 1-7). The MIBI uptake was strongly related to the bone marrow plasma cell infiltration and to cytogenetic abnormalities. Particularly, a MIBI uptake score above 5 identified patients with poor prognosis encompassing all stage III multiple myeloma and three of seven stage II multiple myeloma. On the other hand all stage I and II patients having a MIBI score less than 5 showed a good prognosis. CONCLUSION: Both cytogenetic analysis and a MIBI scan add no relevant prognostic information to the ISS in patients with stage I and III multiple myeloma. The MIBI scan was of prognostic value in stage II multiple myeloma patients. Additionally, MIBI imaging may be useful to guide bone marrow biopsy in order to obtain adequate samples for cytogenetic analysis.

The Crocidura fuliginosa species complex (Mammalia, Insectivora) in Peninsular Malaya: biological, karyological and genetical evidence

Four West Malaysian shrew populations of the genus Crocidura were investigated through their karyotype and allozyme variations, and, in part, by interfertility experiments. Two different karyotypes characterize these shrews. The first, restricted to the Cameron Highlands (Peninsular Malaysia), invariably has 2n = 40 chromosomes but a varying fundamental number (FN = 54-58). The second karyotype shows a fundamental number of 62-68 and a polymorphic chromosomal number of 2n = 38, 39 or 40, a rare event in the genus Crocidura. Thus both can be distinguished by either a low or a higher number of meta- and submetacentric elements. In heterospecific breeding experiments, mutual avoidance was observed suggesting prezygotic barriers, whereas intraspecific pairs produced 13 liters (mean 2.1 young). Furthermore, our biochemical results indicate that both karyotypes correspond to a relatively ancient separation (Nei's D = 0.354), an amount of genetic differentiation comparable to the distance separating them from the West Palearctic C. russula (D = 0.429-0.583). In contrast, conspecific island and mainland Malaysian shrews possessing the second karyotype had only one fixed allelic difference over the 35 loci surveyed. The problem of naming the two biological species remains unsolved and requires further comparative investigations.

Peripheral T-cell lymphoma with t(6;14)(p25;q11.2) translocation presenting with massive splenomegaly.

Recurrent chromosomal translocations associated to peripheral T-cell lymphomas (PTCL) are rare. Here, we report a case of PTCL, not otherwise specified (NOS) with the karyotype 46,Y,add(X)(p22),t(6;14)(p25;q11) and FISH-proved breakpoints in the IRF4 and TCRAD loci, leading to juxtaposition of both genes. A 64-year-old male patient presented with mild cytopenias and massive splenomegaly. Splenectomy showed diffuse red pulp involvement by a pleomorphic medium- to large-cell T-cell lymphoma with a CD2+ CD3+ CD5- CD7- CD4+ CD8+/- CD30- TCRbeta-F1+ immunophenotype, an activated cytotoxic profile, and strong MUM1 expression. The clinical course was marked by disease progression in the bone marrow under treatment and death at 4 months. In contrast with two t(6;14)(p25;q11.2)-positive lymphomas previously reported to be cytotoxic PTCL, NOS with bone marrow and skin involvement, this case was manifested by massive splenomegaly, expanding the clinical spectrum of PTCLs harboring t(6;14)(p25;q11.2) and supporting consideration of this translocation as a marker of biological aggressiveness.