Heterochromatin Regions Of Chromosomes Research Articles

The Missing Link in the Human Thermoregulation Systems

The study of human thermoregulation is one of the most developed areas of modern physiology and medicine. This is due to the important role of temperature in normal and pathological conditions. Directly or indirectly almost all systems and organs are involved in maintaining of relatively constant temperature in the body, since their normal functioning is closely related to the temperature of the internal environment (temperature homeostasis). Currently, the existence of two systems of thermoregulation is recognized: a physiological organ-based system with a center in the hypothalamus and a molecular system, which manifests itself in the form of the production of proteins (heat shock- and cold shock proteins) and by activation of RNA thermometers in response to heat or cold shock. Based on studies of the variability of chromosomal heterochromatin regions in the genome of human populations permanently living in various climatic and geographical conditions of Eurasia and Africa, as well as individuals well adapted to the extreme conditions of the high altitudes of the Pamirs and Tien-Shan (mountaineers) and the Far North (oil drillers of the Yamal Peninsula, Eastern Siberia), we came to the conclusion that, apparently, there is a third system of thermoregulation at the cellular level (cell thermoregulation). By cell thermoregulation, we mean the removal of excess heat from the nucleus of an interphase cell in order to avoid the harmful effects of high temperature on the complex molecular processes occurring in the nucleoplasm. We believe that some intracellular formations (a dense layer of condensed chromatin around the nucleus, nucleoli, chromocenters and other membraneless bodies) serve as a structural basis for the removal of heat from the cell nucleus, because the material basis of all these temporary structures in the interphase nucleus is the chromosomal heterochromatin regions. In this review, we discuss a set of data, which indicate that cell thermoregulation, may be a missing link between organism and molecular level in maintaining temperature homeostasis in the human body.

The origin of the human karyotype: its uniqueness, causes and effects

As is known, the diploid number of human chromosomes is 46, while in other higher primates, such as chimpanzees and gorillas, this number is 48. It has been established that a decrease in the number of chromosomes by two in humans is a result of the fusion of two autosomes into one chromosome in his karyotype ancestors. However, why such changes in chromosomes occurred among the highest primates in humans, their uniqueness, causes and consequences have not yet become the subject of special studies. We believe that the transition from 48 to 46 chromosomes, as well as changes in the composition, localization and amount of chromosomal heterochromatin regions in the karyotype of the ancestors of modern man turned out to be crucial in his formation as a biological species with all the ensuing consequences.

Co-occurrences of polymorphic heterochromatin regions of chromosomes and effect on reproductive failure

Although the polymorphic heterochromatin regions of chromosomes (heteromorphisms) have been extensively studied for their phenotypic effects on humans, co-occurrences of chromosome 1, 9, 16 and Y heteromorphisms and of acrocentric variants have never been studied on humans with an objective scoring system. Here we compared the frequencies of individual heteromorphisms on a total of 602, 768 and 224 patients with the indications of infertility, recurrent miscarriage and in vitro fertilization (IVF) failure, respectively and on 272 controls. Then we examined whether there were significant co-occurrences between heteromorphisms within and between the groups. There were no statistically significant differences in the frequencies of heteromorphisms between the groups. Both statistically significant and non-significant correlations were observed within the non-acrocentric and certain acrocentric heteromorphisms in each group. When these co-occurrences were examined between the groups, a 2.2 fold increased risk of IVF failure in males in the presence of either chromosome 13 or chromosome 21 variants was observed (95 %CI:1.1–4.2). We conclude that the simultaneous manifestations of heteromorphisms have no effect on reproductive failure. There seems to be a correlation between the non-acrocentric heteromorphisms (1qh+, 9qh+, 16qh + and Yqh+/-), which might be the result of complex interactions of formation of these heterochromatin regions. The correlations observed between certain acrocentric chromosomes might be related to satellite association and nucleolus formation. The increased risk observed in males with IVF failure in the presence of either chromosome 13 or 21 variants should be interpreted cautiously due to the heterogeneity of the group.

Mitotic Implantation of the Transcription Factor Prospero via Phase Separation Drives Terminal Neuronal Differentiation.

Compacted heterochromatin blocks are prevalent in differentiated cells and present a barrier to cellular reprogramming. It remains obscure how heterochromatin remodeling is orchestrated during cell differentiation. Here we find that the evolutionarily conserved homeodomain transcription factor Prospero (Pros)/Prox1 ensures neuronal differentiation by driving heterochromatindomain condensation and expansion. Intriguingly, in mitotically dividing Drosophila neural precursors, Pros is retained at H3K9me3+ pericentromeric heterochromatin regions of chromosomes via liquid-liquid phase separation (LLPS). Duringmitotic exit of neural precursors, mitotically retained Pros recruits and concentrates heterochromatin protein 1 (HP1) into phase-separated condensates and drives heterochromatin compaction. This establishes a transcriptionally repressive chromatin environment that guarantees cell-cycle exit and terminal neuronal differentiation. Importantly, mammalian Prox1 employs a similar "mitotic-implantation-ensured heterochromatin condensation" strategy to reinforce neuronal differentiation. Together, our results unveiled a new paradigm whereby mitotic implantation of a transcription factor via LLPS remodels H3K9me3+ heterochromatin and drives timely and irreversible terminal differentiation.

Cell thermoregulation hypothesis: its origin, material basis, mechanisms and meaning

The accumulated knowledge about the chromosome structure, redundant DNA and an interphase nucleus inevitably raises, at least, two questions: (1) Why are there so much non-coding DNAs in chromosomes of higher eukaryotes and (2) what is the role of their organization in interphase nucleus on cellular function? These questions in cell biology are attracting increased attention as the genomes of higher eukaryotes are being sequenced. Based on investigations of chromosomal heterochromatin regions variability in human populations, condensed chromatin (CC), interphase nucleus and redundant non-coding DNAs in the genome, an attempt is made to justify the view of possible participation of CC in cell thermoregulation. CC, being the densest domains in a cell, apparently conducts heat between the cytoplasm and nucleus when there is a difference in temperature between them. Keywords: Cell Thermoregulation; Condensed Chromatin; Q-heterochromatin; C-heterochromatin; Human Body Heat Conductivity; Human Adaptation

Cell thermoregulation and origin of homeothermic animals

Temperature has a fundamental influence in all chemical and biochemical reactions. It influences reaction rates, equilibrium amounts, viscosity, solubility, molecular arrangements and numeric other parameters. Temperature is important for all physiological processes. Maintaining the relative constancy of the internal temperature (temperature homeostasis) is a necessary condition for normal life. Some living beings maintain temperature homeostasis in the body due to external sources of energy (poikilothermy), others due to the energy of food consumption (homeothermy). However, it is unknown the origin of homeothermic organisms. Despite the fundamental similarity of the mechanisms of the central organ-based physiological thermoregulation, even among the higher vertebrates exists poikilothermy and homeothermy animals. It is assumed that homeothermy is not the result of the evolution of physiological mechanisms of thermoregulation. Homeothermy is the result of the evolution of non-coding DNAs in the genome, some of which formed the so-called chromosomal heterochromatin regions (HRs). Chromosomal HRs constitutes the material basis of cell thermoregulation, which is responsible for the removal of excess thermal energy from the nucleus into the cytoplasm. Homeothermic organisms, unlike poikilotherms capable of faster and more efficient leveling of temperature difference between the nucleus and the cytoplasm with all the ensuing consequences.

Cell Thermoregulation: Reality or just a logical Construction?

The existence of biological thermoregulation at the molecular and organism (physiological organ-based system of thermoregulation) levels is well known. The possibility of thermoregulation at the level of individual cells is discussed. By cell thermoregulation (CT) is meant the elimination of the temperature difference between the nucleus and cytoplasm, when, for one reason or another, the level of thermal energy in the nucleus becomes higher than of the cytoplasm. The CT hypothesis can shed light on some scattered facts and observations, known in different areas of biology and medicine, but without rational explanation. It is assumed that CT originated from the evolution of ncDNAs in the eukaryotic genome, and its material basis is condensed chromatin. Although the CT hypothesis has not yet been directly experimentally confirmed, nevertheless, its existence can be determined by indirect methods at the organism level. Keywords: Cell thermoregulation; Condensed chromatin; Chromosomal heterochromatin regions; Human body heat conductivity

Prenatal and Postnatal Clinical Spectrum of a Mosaic Small Supernumerary Marker Chromosome 22

An amniocentesis was performed because of the advanced maternal age at 18 weeks of gestation, and cytogenetic analyses revelaed a de novo mosaic small supernumerary marker chromosome (sSMC), as parental karotypes were normal. Fluorescence in situ hybridization (FISH) analyses with chromosome specific whole chromosome painting, locus, and alphoid satellite DNA probes were ended with the diagnosis of mosaic sSMC of chromosome 22. The result was explained to the family and genetic counselling was given together with the absence of fetal ultrasound findings. The baby was delivered at term by caesarean section. The female neonate with mosaic sSMC did not show any apparent dysmorphic features at birth. No growth and psychomotor retardation were observed at her natal period follow-up. At one year age, she had some mild dysmorphic findings such as high frontal hairline, frontal bossing, thin eyebrows, hypertelorism, flattened tip of nose and prominent philtrum. The reason of the absence of major abnormalities could be related with the presence of heterochromatin region of chromosome 22 rather than the gene rich parts. Finally, this report emphasizes the importance of acting in an analytical algorithm based on chromosomal origin, parental lineage, size and mosaic or non-mosaic status of sSMCs in the prenatal diagnosis, and using FISH technique and postnatal confirmation of the sSMC.

Dynamics of Eukaryotic Histone Exchange with Single Molecule Resolution

Remodelling chromatin structure is important for regulating gene expression, DNA replication and repair and other fundamental nuclear processes. The basic chromatin unit is the nucleosome. SWR1 is a multi-subunit complex, whose chromatin remodelling activity is associated with regulation of gene expression in heterochromatin regions of chromosomes in plants and mammals, and with the cellular response to DNA damage. In yeast, the simplest eukaryotic organism, the SWR1 complex is responsible for the ATP-dependent nucleosome remodelling by exchanging its canonical H2A histone with Htz1 variant (also known as H2A.Z in mammalian cells). In spite of a large number of genetic, biochemical and structural studies on SWR1, its detailed histone exchange mechanism remains largely unknown. To investigate the mechanism of histone exchange by SWR1, we have developed a single-molecule FRET assay, which monitors the interaction between individual nucleosomes and yeast SWR1 complexes in real time. The data show distinct dynamic behaviours in the presence or absence of ATP, or in the presence of non-hydrolysable ATP analogue. We hypothesize that the observed dynamics are important for the removal of canonical H2A histones or deposition of the histone variant Htz1. We anticipate that our data will help elucidate the molecular mechanism of histone exchange by SWR1.

Cell Thermoregulation: Problems, Advances and Perspectives

Thermoregulation at organism level is the well-established fact. The question on possibility of thermoregulation at the cell level remains opened. Based on study of distribution of chromosomal heterochromatin regions (HRs) in various human populations, in norm and at some forms of pathology the hypothesis about thermoregulation existence at the cell level has been presented. The essence of hypothesis of cell thermoregulation (СТ) is elimination of the temperature difference between the nucleus and cytoplasm when the nucleus temperature becomes higher than the cytoplasm temperature. The nucleus, in contrast to the cytoplasm, cannot conduct heat directly in the extracellular space, from where the heat is taken by the circulating flow of sap, lymph and blood. Thus, the nucleus can conduct heat only in the cytoplasm. With this, the nucleus has two options for the dissipation of heat surplus: either by increasing its volume or increasing the heat conductivity of the nuclear envelope. As the first option is limited, and the second one is hampered because of thickness of the cell membranes, apparently the higher eukaryotes took advantage of the opportunity of a dense layer of peripheral condensed chromatin (CC) as heat conductor for a more efficient elimination of the temperature difference between the nucleus and cytoplasm. The СС localized between a nucleus and cytoplasm is made of different types of chromosomal HRs. For this reason, СС is subject to wide variability in population. Obviously, the density of the СС packing depends on the type and quantity of chromosomal HRs in its structure that can affect upon its heat-conducting ability. If the situation is this then we are entitled to expect a new type of variability with all consequences resulting from here.

The effects of a heterochromatin polymorphism in chromosome 6 on premature ovarian failure

Abstract Through cytogenetic analysis, heteromorphisms were detected in chromosomes 1,9,16 and Y and defined as non-phenotypic variations. The polymorphism in the centromeric heterochromatin region of chromosome 6 is a rare variant, and only five cases have been documented in the literature. In our study, we used cytogenetic and molecular techniques to detect an increase in the centromeric heterochromatin region in the short arm of both copies of homologous chromosome 6 in a premature ovarian failure (POF) case. The report of this case is important for determining the relationship between fertility and the frequency of rare variants of the centromeric heterochromatin region of chromosome 6 in the general population.

Chromosome studies on two endemic pill-millipedes of the genus Arthrosphaera (Diplopoda: Sphaerotheriida) from the Western Ghats of India

The diploid chromosome number of pill-millipedes (Class, Diplopoda) varies between 16 (Glomeridae) and 30 (Arthrosphaeridae) with XY pattern of sex determination. The meiotic division stages and karyotype of chromosomes derived from the spermatogonial metaphase of two pill-millipedes Arthrosphaera craspedota and A. lutescens of the Western Ghats of India revealed the diploid chromosome number 30 and 26, respectively. The meiotic chromosome behavior was almost similar in these species. The zygotene in A. craspedota consists of bouquet formation, the diplotene bivalents exhibited characteristic fuzziness and the sex bivalents were conspicuous with terminal chiasma. Deeply stained heterochromatin regions in chromosomes and conspicuous sex bivalents were seen in A. lutescens. Autosomes as well as sex chromosomes were acrocentric with relative length range was 20.6–170.1 in A. craspedota, while 27.6–145.2 in A. lutescens. It is believed that the acrocentric nature of chromosomes in Arthrosphaera was the result of Robertsonian changes, pericentric inversions and polyploidy. Recent studies revealed that the Malagasy-Indian genus Arthrosphaera evolved between 160 and 80 mya (breakup of Madagascar and India). Cytological investigations on endemic Arthrosphaera (A. brandtii) and its sister taxon Sphaeromimus distributed in the Madagascar may provide more insight on the chromosomal evolutionary pattern in pill-millipedes.

Peculiarity of mitotic activity of chorionic villi cytotrofoblast on the first trimester of pregnancy

Mitotic activity of chorionic villi cytotrophoblast of the 1st trimester at normal and missed pregnancy was studied. Proliferative activity of cytotrophoblast from missed abortions was somewhat increased in vitro. Application of a semidirect method of chromosomal preparation from chorionic villi is more efficient and provides better resolution for cytogenetic diagnostics of missed abortion. Unusual peculiarity in organization and replication of pericentric heterochromatin regions of chromosomes 1, 9 and 16 was detected

Phenomenon of selective staining of pericentromeric heterochromatin regions in chromosomes from spontaneously dividing cells by the acridine orange fluorochrome

A novel phenomenon of unusual selective acridine orange (AO) staining of pericentromeric heterochromatin regions (HRs) in chromosomal preparations from tissue with known spontaneous mitotic activity (chorionic villi, placenta, embryonic tissues, bone marrow, and testes), as well as embryonic stem cells, is described. Staining with 0.01% AO in a citric-phosphate (pH 5.5) or sodium phosphate (pH 7.0) buffer solution allows the HRs of human chromosomes (1q12, 9q12, 13p11.2, 14p11.2, 15p11.2, 16q11.2, 21p11.2, 22p11.2, and Yq12) and pericentromeric HRs of mouse chromosomes to be reliably detected by the red fluorescence of AO. This method of AO staining does not require any pretreatment. Explanations for metachromatic AO staining of polymorphic pericentromeric HRs in chromosomes of spontaneously dividing cells are suggested. A high reproducibility of the specific AO staining makes it possible to suggest its using as a reliable quick method for detection of polymorphic HRs of human chromosomes in cytogenetic prenatal diagnosis and oncohematology.

Characterization of Cyclops kolensis inter-simple sequence repeats in germline and postdiminution somatic cells

337 Chromatin diminution is programmed elimination of a part of the genome from presumptive somatic cells during early embryogenesis of some animal species. Chromatin diminution was described for a fairly small number of species of different groups of animals, such as ascarides, myxines, dipterans, Cyclops , and protozoans [2, 3, 6, 8, 10, 13, 14]. Although a great variety of chromatin diminution forms is known, it seems most promising to study this process in Cyclops kolensis Lill., a member of the family Cyclopidae. This freshwater crustacean contains a record-breaking (~94%) amount of eliminated DNA (eDNA) compared to other multicellular animals. In this species, DNA is eliminated from chromosomes of somatic cells during the fourth cleavage division, with the diploid chromosome number remaining unchanged [2, 3]. In this study, we demonstrated that chromatin diminution in C. kolensis is not accompanied by total elimination of nonfunctional genomic regions. This finding broadens our notion on chromatin diminution in C. kolensis . Currently, the molecular mechanisms ensuring diminution and determine the eDNA type remain largely obscure. However, it was shown that the C. kolensis eDNA contains noncoding sequences, some of which have an intricate mosaic structure of repeats [7]. It is known that Mesocyclops edax , another member of the family Cyclopidae, loses a considerable part of satellite DNA sequences during chromatin diminution [9]. The so-called microsatellite sequences are also classified with the satellite DNA. Microsatellite, or short tandem repeats (simple sequence repeats, SSRs), are a characteristic component of the eukaryotic genome. Today, an ample body of evidence regarding the structure of this component and the mechanisms that ensure their size polymorphism and increase in the number of their copies has been accumulated [15]. The consistent patterns of microsatellite distribution over the genome has been studied and their predominant concentration in the noncoding region of the genome has been shown [11]. An average distance between microsatellites in heterochromatin regions varies from several hundreds to several thousands of nucleotide pairs [12], which makes it possible to amplify the DNA fragments located between microsatellites (the so-called inter-simple sequence repeats, or ISSRs sequences) by polymerase chain reaction (PCR). It was shown earlier that, in some species, the majority of heterochromatin regions in chromosomes is eliminated from the genome of somatic cells in the course of chromatin diminution [10, 13]. It can be assumed that a considerable part of heterochromatin, including the microsatellite sequences, is eliminated from the C. kolensis genome during chromatin diminution. In this study, we amplified, cloned, and sequenced five C. kolensis DNA sequences located between the (GA) n microsatellite sequences. A comparative analysis of the nucleotides comprising the cloned sequences was performed using special software programs. Unique internal primer pairs selected for four out of five cloned sequences made it possible to amplify by PCR the corresponding DNA fragments initially located between the (GA) n microsatellites. We performed a comparative analysis of the amplification products of these sequences in C. kolensis before and after chromatin diminution. It was found that three out of four intermicrosatellite loci studied remain in the genome of somatic cells after chromatin diminution and only one of them is eliminated during diminution. Female C. kolensis caught in the pond situated on Vorob’evy Gory (Moscow) were determined according to Monchenko [4]. The prediminution stage of

Variability in the heterochromatin regions of the chromosomes and chromosomal anomalies in children with autism: Identification of genetic markers of autistic spectrum disorders

Cytogenetic and molecular cytogenetic analysis of children with autism (90 subjects) and their mothers (18 subjects) is presented. Anomalies and fragility were found in chromosome X in four cases of autism: mos 47,XXX[98]/46, XX[2]; 46,XY,r(22)(p11q13); 46,XY,inv(2)(p11.2q13),16qh-; and 46,Y,fra(X)(q27.3),16qh-. C staining and quantitative fluorescent in situ hybridization (FISH) were used to demonstrate a significant increase in the frequency of variations in the heterochromatin regions of chromosomes in children with autism as compared with a control group (48% and 16% respectively). Pericentric chromosome inversion 9phqh was not characteristic of patients with autism, while variation in heterochromatin regions 1phqh, 9qh+, and 16qh-were found significantly more frequently in children with autism. These data provide the basis for discussing the possible role of the gene position effect in the pathogenesis of autism and the possible search for biological markers of autistic disorders.

Detection of Y chromosome loss by fluorescence in situ hybridization in pancreatic cancer

To investigate the correlation between loss of Y chromosome and development of pancreatic cancer. The status of Y chromosome was analyzed by two color interphase fluorescence in situ hybridization. performed on paraffin sections of pancreatic cancer tissues from 15 Chinese males. The probes located on the heterochromatin region of chromosome Y (maps to Yq12) and on the alpha satellite of X chromosome (maps to centromeric region) were selected for testing and as control respectively. The cancer cells from 10 out of the 15 pancreatic cancer patients studied showed loss of chromosome Y. The Y chromosome in the cells of surrounding non-neoplastic pancreatic tissues was intact. Loss of chromosome Y occurs non-randomly in tumor cells of Chinese male patients with pancreatic cancer. This cytogenetic aberration, which happens in high frequency, may serve as one of the markers for pancreatic malignancy.

Chromosome aberrations in a schizophrenia population

Cytogenetic abnormalities with schizophrenia may provide a valuable clue to the identification of target loci and successful search for major genes. We have performed chromosomal examinations by using the GTG banding technique on 134 schizophrenics. In 43 patients (32%), random numerical and structural aberrations were detected. Structural aberrations predominated and usually consisted of deletions and inversion of various chromosomes. Numerical changes were present in one or two cells in 14 cases including trizomy 21, marker and acentric chromosomes, and 47,XXY. The seven cases with pericentric inversion and enlargement of the heterochromatin region of chromosome 9 (inv(9); 9qh+) were observed in the study. The incidence (5.2%) of inv(9) and 9qh+ in our schizophrenic patients were found higher than the general population, suggesting that a susceptibility locus for schizophrenia may be located at pericentromeric region of chromosome 9. Our study have detected 1q21, 7q23, inv(9), 9qh+, 11q23, 21q22, 22q11-13 and Xp11-q13 suggested that these chromosomal lesions are prevalent in schizophrenics. The reason for this might be that these anomalies increase risk for schizophrenia in a relatively nonspecific way, such as contributing to disruption of normal embryogenesis of the nervous system.

A cytogenetic study in 120 Turkish children with intellectual disability and characteristics of fragile X syndrome.

We review the evidence for the frequency of the fragile X syndrome (FXS), other X-linked abnormalities, and other chromosomal disabilities of Turkish pediatric psychiatry outpatients with intellectual disability. Reported clinical features and genetic findings were used in cytogenetic screenings to estimate the prevalence of the fragile X (fra X) and other chromosomal aberrations in 120 patients with mental retardation, language disorders, attention deficit hyperactivity, or developmental delay, in comparison with 30 healthy children. Data on the clinical, intellectual and behavioral findings in 14 fra X positive children (11.7%) is presented. Ten of the 120 patients (8.3%) had enlargement of the heterochromatin region of chromosome 9. Other chromosomal aberrations and autosomal fragile sites (FS) were also observed. There was a statistically significant difference in the autosomal and X-linked FS between the study and control groups (p < 0.05). The tests for the fra X chromosome are likely to be of diagnostic benefit in young children with autism or developmental delay, particularly in speech, and who have large and prominent ears.

Correlation of DNA Hypomethylation at Pericentromeric Heterochromatin Regions of Chromosomes 16 and 1 with Histological Features and Chromosomal Abnormalities of Human Breast Carcinomas

Changes in DNA methylation status are not only important for regulating gene expression but are also suggested to induce chromosome instability. To reveal the correlation of DNA methylation status in heterochromatin regions with tumor histology and with chromosome alterations, DNA methylation status was examined by Southern blot analysis, and numerical and structural chromosome alterations, including the formation of der(16)t(1;16)/der(1;16), were examined by fluorescence in situ hybridization at the two loci in the pericentromeric satellite 2 regions of chromosomes 16 and 1 in 39 human breast carcinomas. DNA hypomethylation at the D16Z3 and the D1Z1 loci was detected in 31% (12 of 39) and 36% (12 of 33) of carcinomas, respectively, and mostly concurred. DNA hypomethylation was more frequent in the carcinoma group of more aggressive histological types or grade 3 than in the carcinoma of less aggressive histological types or grades 1 and 2, and tended to be more frequent in carcinomas with > or =4 copies of chromosomes 16 and/or 1 than in carcinomas with < or =3 copies of any of these chromosomes. The frequency of DNA hypomethylation at the D16Z3 and the D1Z1 loci was 45% (10 of 22) and 53% (9 of 17) in carcinomas without der(16)t(1;16)/der(1;16), formation, but only 12% (2 of 17) and 19% (3 of 16) in carcinoma with der(16)t(1;16)/der(1;16), respectively (P = 0.036 and 0.070). The 16q breakage was almost equally detected between carcinoma groups with and without the DNA hypomethylation. DNA hypomethylation in the satellite 2 regions was suggested to be associated with the accumulation of a large number of numerical chromosome alterations and involved in the development of breast carcinomas of aggressive histological features. On the contrary, chromosome instability induced by mechanisms other than DNA hypomethylation in heterochromatin regions might cause the formation of der(16)t(1;16)/der(1;16) and less aggressive breast carcinomas.