Identification of cryptic structural chromosomal aberrations in parents through detection of copy number variations in miscarriage tissues / 中华医学遗传学杂志

Objective@#To explore the genetic cause for abnormal pregnancies through detecting chromosomal copy number variations (CNVs) in abortic tissues by next generation sequencing (NGS).@*Methods@#NGS technique was used to detect CNVs in abortion tissues. Parental chromosomal karyotypes were predicted based on the results. The aberrant chromosomal segments of the parents were accurately mapped by G-banding karyotyping analysis and fluorescence in situ hybridization (FISH).@*Results@#In addition to numerical chromosomal aberrations, 12 microdeletion/microduplications were detected by NGS. For 8 families where both parents accepted chromosomal karyotyping, 4 carriers of chromosomal abnormalities were identified. One marker chromosome was missed by karyotyping analysis, and a mother was confirmed to carry a cryptic balanced translocation by FISH.@*Conclusion@#NGS can facilitate detection of cryptic chromosomal translocations in couples with repeated pregnancy failure and is of great value for detecting abnormal CNVs for its high sensitivity.

Effects of different controlled ovarian stimulation protocols on preimplantation genetic testing outcomes of chromosomal translocation carriers / 中国实用妇科与产科杂志

OBJECTIVE: To investigate the effects of GnRH agonist and antagonist protocols on preimplantation genetic testing outcomes of chromosomal translocation carriers.METHODS: The clinical data of 226 patients with chromosomal translocation were analyzed retrospectively between Jan. 2015 and Dec. 2017 in Shengjing Hospital Affiliated to China Medical University.The patients were divided into GnRH agonist group(174 cases)and GnRH antagonist group(52 cases),then the duration of gonadotropin stimulation,dosage of gonadotropin used,embryonic quality,normal and balanced embryo numbers,per transfer cyclepregnancy rate,abortion rate and continuous pregnancy rate and accumulated pregnancy rate were analyzed.RESULTS: There were no statistical differences in the number of retrieved oocytes,number of MⅡ oocytes,fertilization rate,cleavage rate,blastocyst formation rate,number of high-quality embryo,number of blastocyst biopsy,normal and balanced embryo numbers,per transfer cycle pregnancy rate,abortion rate,continuous pregnancy rate or accumulated pregnancy rate between GnRH agonist group and GnRH antagonist group(P>0.05).The duration of gonadotropin stimulation(9 d vs. 10 d)and dosage of gonadotropin(2100 U vs. 2400 U)used in the GnRH antagonist group were significantly less than the GnRH agonist group(P<0.05).CONCLUSION: There are no significant differences in embryo quality or pregnancy rate between the GnRH agonist group and antagonist group during preimplantation genetic testing,but the GnRH antagonist group have an advantage in Gn duration and dosage.

FusionScan: accurate prediction of fusion genes from RNA-Seq data

Identification of fusion gene is of prominent importance in cancer research field because of their potential as carcinogenic drivers. RNA sequencing (RNA-Seq) data have been the most useful source for identification of fusion transcripts. Although a number of algorithms have been developed thus far, most programs produce too many false-positives, thus making experimental confirmation almost impossible. We still lack a reliable program that achieves high precision with reasonable recall rate. Here, we present FusionScan, a highly optimized tool for predicting fusion transcripts from RNA-Seq data. We specifically search for split reads composed of intact exons at the fusion boundaries. Using 269 known fusion cases as the reference, we have implemented various mapping and filtering strategies to remove false-positives without discarding genuine fusions. In the performance test using three cell line datasets with validated fusion cases (NCI-H660, K562, and MCF-7), FusionScan outperformed other existing programs by a considerable margin, achieving the precision and recall rates of 60% and 79%, respectively. Simulation test also demonstrated that FusionScan recovered most of true positives without producing an overwhelming number of false-positives regardless of sequencing depth and read length. The computation time was comparable to other leading tools. We also provide several curative means to help users investigate the details of fusion candidates easily. We believe that FusionScan would be a reliable, efficient and convenient program for detecting fusion transcripts that meet the requirements in the clinical and experimental community. FusionScan is freely available at http://fusionscan.ewha.ac.kr/.

Trisomy 21 with t(5;11) Chromosomal Translocation as New Unfavorable Cytogenetic Abnormalities in Pediatric Acute Myeloid Leukemia Type M2: One Case Report of Nine-year Follow-up and Literature Review / 华中科技大学学报（医学）（英德文版）

We report one case of pediatric acute myeloid leukemia type 2 (AML-M2) who presented with karyotypic aberration of trisomy 21 with the t(5;ll) chromosomal translocation.The patient achieved complete remission after two cycles of chemotherapy of daunorubicin,cytarabine and etoposide.Then,follow-up cytogenetic analysis from bone marrow cell cultures demonstrated a normal karyotype of 46,XY.After 9 years,the patient relapsed and the karyotypic abnormalities of trisomy 21 with t(5;ll) reappeared.It was concluded that trisomy 21 with t(5;11) is a new unfavorable cytogenetic aberration in AML-M2.

A Case Report of Concurrent IDH1 and NPM1 Mutations in a Novel t(X;2)(q28;p22) Translocation in Acute Myeloid Leukaemia without Maturation (AML-M1)

Acute myeloid leukaemia (AML) is one of the fatal haematological malignancies as a consequence of its genetic heterogeneity. At present, the prediction of the clinical response to treatment for AML is based not only on detection of cytogenetic aberrations but also by analysing certain molecular genetic alterations. There are limited in sights into the contribution, disease progression, treatment outcome, and characterisation with respect to the uncommon chromosomal abnormalities leading to AML. Here, we describe the clinical, morphological, cytogenetic, and mutational findings of a 52-year-old female patient with AML without maturation (AML-M1). Conventional karyotyping and spectral karyotyping (SKY) were done on metaphase chromosomes from bone marrow cells at the time of diagnosis. A mutation analysis was performed on the hotspot regions of various genes, including FLT3, CEBPA, NPM1, RAS, c-KIT, IDH1 and IDH2. Cytogenetic and mutation analyses revealed a novel translocation, t(X;2)(q28;p22), with both NPM1 and IDH1 mutations. To the best of our knowledge, the presence of both NPM1 and IDH1 mutations in t(X;2) (q28;p22) is a novel finding in AML.

Unexpected Inheritance of a Balanced Homologous translocation t(22q;22q) from father to a phenotypically normal daughter.

Rearrangements between homologous chromosomes are extremely rare and manifest mainly as monosomic or trisomic offsprings. There are remarkably few reports of balanced homologous chromosomal translocation t (22q; 22q) and only two cases of transmission of this balanced homohologous rearrangement from mother to normal daughter are reported. Robersonian translocation carriers in non‑homologous chromosomes have the ability to have an unaffected child. However, it is not possible to have an unaffected child in cases with Robersonian translocations in homologous chromosomes. Carriers of homologous chromosome 22 translocations with maternal uniparental disomy do not have any impact on their phenotype. We are presenting a family with a history of multiple first trimester miscarriages and an unexpected inheritance of balanced homologous translocation of chromosome 22 with paternal uniparental disomy. There are no data available regarding the impact of paternal UPD 22 on the phenotype. We claim this to be the first report explaining that paternal UPD 22 does not impact the phenotype.

Relationship between gene positioning and chromosomal translocation in cancer / 肿瘤

Chromosomal translocations are very common in human cancer. The molecular mechanisms of chromosomal translocations are complex and unclear. Recent studies show that the organization of genomes is higher-order in the nucleus and every chromosome or chromatin has its preferential position and territory. Intermingling of chromosome territories in interphase maintains the transcriptional networks of genes. The spatial arrangements of chromosomes and gene loci in the interphase nucleus are responsible for nonrandom chromosomal translocations in human cancer. Chromosomal translocations are favored in neighbor chromosomes or genes in spatial proximity within the nucleus. These findings may lead to new approaches in early diagnosis and target therapy of cancer. © 2012 by Tumor.

A Case of Acute Promyelocytic Leukemia with a De novo t(11;19) Chromosomal Translocation / 대한내과학회지

Acute promyelocytic leukemia (APL), which is usually defined by the morphological features of the leukemic cells, is characterized by the t(15;17) (q22;q21) chromosomal translocation and disseminated intravascular coagulation. This specific translocation results in a new fusion transcript between the promyelocytic leukemia (PML) gene and the retinoic acid receptor-alpha (RARalpha) gene. Although the presence of this fusion gene can predict a favorable clinical response to all-trans-retinoic-acid (ATRA) treatment, APL with chromosomal translocations other than t(15;17) (q22;q21) is extremely rare and is associated with a poor prognosis. We experienced a case of APL with de novo t(11;19).

Molecular Genetic Approach of Gastric MALT Lymphoma

Mucosa-associated lymphoid tissue (MALT) lymphoma is a common low grade B-cell lymphoma arising from a background of chronic inflammatory disease at a number of mucosal sites. The association between Helicobacter pylori and gastric MALT lymphoma is well known and it appears that H. pylori is critical for lymphomagenesis and also creates a microenvironment favoring the growth of neoplastic B cells. The understanding of MALT lymphoma biology has significantly improved, and at least 4 recurrent translocations t(11;18)/API2-MALT1, t(1;14)/IGH-BCL10, t(14;18)/IGH-MALT1 and t(3;14)/IGH-FOXP1 have been implicated in the pathogenesis of MALT lymphoma. Here, we review the recent advances in association of microorganisms with MALT lymphoma and the molecular genetics underlying the lymphoma development.

Identification of 2nd chromosome region translocated onto the W chromosome by RFLP with EST-cDNA clones in the Gensei-kouken strains of the mulberry silkworm, Bombyx mori L

In silkworms, sex-limited strains are either obtained spontaneously or induced by X-rays or gamma rays. When a fragment of an autosome carrying a dominant allele of those genes responsible for certain characters is translocated onto a W chromosome, the female of the successive generations will express these phenotypic characters and sex discrimination can be facilitated. Gensei-kouken strains are sex-limited strains of silkworms developed by irradiating the pupae with gamma rays, by which a portion of the second chromosome is translocated onto the W chromosome. In these improved strains, the females are yellow-blooded and spin yellow cocoons. By using the EST-cDNA clones mapped on the Z chromosome, we identified the sex according to the polymorphic banding pattern or intensity of the signals. Furthermore, by using the clones on the second chromosome, the region of the second chromosome translocated onto the W chromosome was also defined. In both the A95 and A 96 strains selected for the present study, only the mid-portion of the second chromosome was translocated. The differences in length of the fragments translocated in these strains are discussed.

A Case of Acute Promyelocytic Leukemia with PML/RARA Translocation Showing Familial t(9;15)(q34;q22)

We report the unusual case of an APL patient with a familial t(9;15)(q34;q22) and acquired t(15;17) (q22;q21). This is unique in that the patient had a constitutional abnormality with the same breakpoints as those observed in the tumor clone from the APL. It is unclear if the breakpoint, 15q22, in the constitutional aberration influenced the induction of the PML/RARA translocation in the APL. If a specific translocation in a patient with leukemia does not go away with clinical improvement, a congenital or familial chromosomal abnormality should be considered. Additional patients with similar findings are needed to understand the pathogenesis of these events.

ChimerDB - Database of Chimeric Sequences in the GenBank

Fusion proteins resulting from chimeric sequences are excellent targets for therapeutic drug development. We developed a database of chimeric sequences by examining the genomic alignment of mRNA and EST sequences in the GenBank. We identified 688 chimeric mRNA and 20,998 chimeric EST sequences. Including EST sequences greatly expands the scope of chimeric sequences even though it inevitably accompanies many artifacts. Chimeric sequences are clustered according to the ECgene ID so that the user can easily find chimeric sequences related to a specific gene. Alignments of chimeric sequences are displayed as custom tracks in the UCSC genome browser. ChimerDB, available at http://genome.ewha.ac.kr/ECgene/ChimerDB/, should be a valuable resource for finding drug targets to treat cancers.

Fusion of the PLAG1 and CTNNB1 genes in pleomorphic adenoma of the salivary glands

The pleomorphic adenoma is the most common neoplasm involving both the major and minor salivary glands. It is a benign, slowgrowing tumor, but local recurrences can occur. The pleomorphic adenoma gene 1 (PLAG1), which is a novel zinc finger gene, is frequently activated by reciprocal chromosomal translocations involving 8q12 in a subset of salivary gland pleomorphic adenomas. This experimental study was preformed to observe the translocation patterns between PLAG1 gene and the three translocation partner genes. We also have analyzed the presence of PLAG1 transcripts by RT-PCR. CTNNB1/PLAG1 gene fusion was observed in three of nine pleomorphic adnomas. However, LIFR/PLAG1 and SII/PLAG1 gene fusions were not detectable. All of three gene fusions was not detectable in one Warthin's tumor and three inflammatory salivary gland tissues. PLAG1 transcripts were expressed in all inflammatory salivary gland tissues and tumors except for three pleomorphic adenomas. Of particular one pleomorphic adenoma showing CTNNB1/P AG1 gene fusion did not express PLAG1 transcipt. Our data indicate that gene fusion involving PLAG1 is a frequent event in pleomorphic adenoma, but correlation between gene fusion involving PLAG1 and PLAG1 transcription is not definite.

Relationship between chromosomal translocation and synovial sarcoma / 中国癌症杂志

Synovial sarcoma is a high grade malignant soft tissue tumor. Its diagnosis and differential diagnosis are difficult. In most cases the reciprocal chromosomal translocation between chromosome X and chromosome 18 could be found and characterized synovial sarcoma. This article reviewed the relationship between chromosomal translocation and the diagnosis, histological type and prognosis of synovial sarcoma.

Demographic and cytogenetic study in recurrent spontaneous aborters.

Chromosomal analysis was performed in a series of 30 women with repeated spontaneous abortions and their husbands. Out of the 30 women, one woman of age 28 years with history of spontaneous abortions was detected to be a chromosomal mosaic 46,XX/47,XXX and with corresponding sex chromatin positive picture C +ve / ++ve. She had normal phenotype and spontaneous abortions that occurred in the second/third months of pregnancy. Her husband was normal and has normal karyotype (46,XY).

The incidence of fetal chromosomal abnormalities in recurrent miscarriage couples with balanced translocation / 대한산부인과학회잡지

OBJECTIVES: The most common chromosomal abnormality contributing to recurrent abortion is the balanced chromosomal translocation. However the exact incidence of fetal losses are still unknown. The objectives of this study were to evaluate the incidence of fetal chromosomal abnormalities and outcome of pregnancy in recurrent miscarriage couples with balanced translocation. DESIGN: A retrospective analysis of recurrent spontaneous abortion patients with balanced chromosomal translocation. MATERIALS AND METHODS: Cytogenetic analysis was performed in 56 couples with history of recurrent abortions from 1995 to 1999. The use of high resolution banding technique and fluorescent in situ hybridization (FISH) in the chromosomal analysis has made the precise evaluation of chromosome aberrations. RESULTS: Among 56 couples, 42 patients had reciprocal translocation and 14 had Robertsonian translocation. Chromosomal aberrations were more frequent in women (36 cases) than in men (20 cases). Prenatal cytogenetic analyses were carried out in 14 subsequent pregnancies for carrier couples with balanced translocation. The fetal karyotypes showed that 5 cases (35.7%) was normal, 8 (57.1%) were balanced translocation, and 1 (7.1%) was unbalanced translocations. And cytogenetic analyses were done on 15 subsequent chorionic villi samples of abortuses for carrier couples with balanced translocations. Fourteen of fifteen abortuses (93.3%) were abnormal karyotype. CONCLUSIONS: Although the incidence of chromosomal imbalance in the fetuses was relatively low in prenatal cytogenetic analysis, individuals with balanced translocations are predisposed to giving birth to malformed offsprings with chromosomal imbalance (partial trisomy or monosomy). Therefore we recommend preimplantation genetic diagnosis (PGD) for recurrent abortions with balanced translocation and preventing the birth of offspring with chromosomal abnormalities.