Research Advances in Multiple Myeloma with Chromosome 1q21 Amplification / 中国实验血液学杂志

Multiple myeloma (MM) is a kind of hematologic malignancy occurring in plasma cells. Cytogenetic technique plays an important role in risk stratification of MM. 1q21 amplification is one of the common chromosomal abnormalities in MM. Studies have shown that 1q21 amplification is associated with poor prognosis in MM patients. At present, with the development of new drugs, cellular immunotherapy, and improvement of hematopoietic stem cell transplantation technology, the remission depth and survival time of MM significantly increased. Rapid and accurate identification of high-risk patients and individualized treatment according to the patient's condition is the key to improve the therapeutic effect of MM. This article reviews the mechanism of 1q21 amplification in MM and the efficacy of new drugs in the treatment of MM with 1q21 chromosome amplification.

Pleomorphic Xanthoastrocytoma with Oligodendroglioma-Like Areas with Negative 1p19q Co-Deletion

The most common mixed glioma encountered in routine surgical practice is oligoastrocytoma (OA); however, its is currently considered a vanishing entity. The 2016 classification of the World Health Organization (WHO) discourages the diagnosis of tumors as mixed glioma. The recommendations are that diffuse gliomas, including those withmixed or ambiguous histological features, should be subjected tomolecular testing. Dual-genotype OAs are not yet a distinct entity or variant in the classification. We report a case ofmixed glioma: a pleomorphic xanthoastrocytoma (PXA)mixed with an oligodendroglioma. The immunohistochemistry (IHC) pattern of isocitrate dehydrogenase 1 (IDH1) negativity with retained nuclear expression of the alpha-thalassemia x-linked intellectual disability syndrome (ATRX) protein, and 1p19q co-deletion negativity in both the components enabled its identification as a mixed glioma rather than a collision tumor. To the best of our knowledge, the case herein presented is the fourth case of PXA with oligodendroglioma. Out of the other three reported cases, only one was of a collision tumor with a dual genotype, and the other two showed similar molecular signatures in both components. The present article discusses the histological, immunohistochemical and molecular features of the aforementioned case.

Analysis of a family with recurrent fetal copy number variations in 1p31.1 / 中华医学遗传学杂志

OBJECTIVE@#To analyze a family with recurrent fetal copy number variations (microdeletion and microduplication, respectively) of 1p31.1 using single nucleotide polymorphism-based array (SNP-array) and G banding chromosomal karyotyping.@*METHODS@#Amniocentesis and chorionic villus sampling were performed for a woman during the two pregnancies. Whole genome SNP-array was used to detect genomic imbalance of the fetus. The couple was also subjected to G-banding chromosomal analysis and SNP-array analysis.@*RESULTS@#SNP-array showed a 1p31.1 (70 164 686-83 474 843) ×1 and a 1p31.1 (70 164 686-83 479 747) ×3 in the fetuses during the two pregnancies, respectively. SNP array results of the couple appeared to be normal. The mother of the fetuses had a 46,XX,inv(1)(p31.1p32.1) karyotype.@*CONCLUSION@#The paracentric inversion in chromosome 1 in the gravida probably underlies the recurrent 1p31.1 copy number variations in the fetuses. SNP-array combined with G banding chromosomal analysis are suitable for prenatal diagnosis for recurrent microdeletion and microduplication in the same chromosomal region, and can provide detailed information for genetic counseling.

Clinical Features and Therapeutic Efficacy in Adult Acute Lymphoblastic Leukemia with t (1; 19) (E2A-PBX1) / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical features and therapeutic efficacy in adult ALL patients with t (1; 19) (E2A-PBX1).@*METHODS@#The clinic data of 19 adult ALL patients with t (1; 19) (E2A-PBX1) in our hospital from Nov. 22, 2010 to Apr. 4, 2018 were collected. The clinical features,complete remission (CR) rate, overall survival (OS) rate and relapse-free survival (RFS) rate of patients received chemotherapy and chemotherapy+HSCT were analyzed.@*RESULTS@#In all the 19 patients, the median age was 24 (14-66), median WBC count was 16.47×109 (1.8-170.34)/L, median Hb level was 98 (65-176) g/L, median Plt count was 50 (15-254)×109/L. Pre B-ALL were 17 cases (89.5%), and common B-ALL were 2 cases (10.5%). Patients received the induction therapy, the overall CR rate was 94.7%, one course CR rate was 94.7%, 4 year OS rate was 47.1% and RFS rate was 43.3%. The OS rate and RFS rate of patients received transplantation were slightly higher than those of patients not received transplantation (OS: 62.5% vs 36.7%) (P=0.188)；RFS (62.5% vs 38.9%) (P=0.166).@*CONCLUSION@#Most adult ALL patients with t (1; 19) (E2A-PBX1) is Pre B-ALL by Immunophenotyping, as compared with the pediatric patients, the therapeutic efficacy for adult patients with t (1; 19) (E2A-PBX1) is worsen, therefore, stem cell transplantation is still acquired for better long term survival.

Phenotypic and genetic analysis of a boy with partial trisomy of 1q / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To delineate the nature and origin of chromosomal aberration in a boy with mental retardation and multiple congenital deformities.</p><p><b>METHODS</b>The karotypes of the proband and his parents were analyzed with routine G-banded chromosomal analysis. Genomic DNA was also analyzed with array comparative genomic hybridization (aCGH) assay.</p><p><b>RESULTS</b>The karyotype of the proband was 46,XY,add(1)(p36.3). No karyotypic abnormality was detected in either parent. aCGH has identified a de novo 25.1 Mb duplication at 1q42q44 in the proband.</p><p><b>CONCLUSION</b>The de novo 1q42q44 duplication, which may be due to non-allelic homologous recombination mediated by low copy repeats, probably underlies the abnormalities in the proband.</p>

Prenatal diagnosis of two fetuses with chromosome 1p36 deletion syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze two fetuses with multiple malformations revealed by ultrasonography using single nucleotide polymorphism array (SNP array), and to explore the strategy for the prenatal diagnosis of 1p36 deletion syndrome.</p><p><b>METHODS</b>Amniocentesis was performed on the two pregnant women. Amnion fluid cells were cultured, and karyotypes of the fetuses were determined through G-banding analysis. Whole genome SNP array was used to detect genomic anomalies of the two fetuses. The karyotypes of their parents were determined through G-banding analysis of peripheral venous blood samples.</p><p><b>RESULTS</b>G-banding analysis showed a 46,XY,add(1p36)? and a 46,XX,add(1p36)? karyotype for fetuses 1 and 2, respectively. SNP array analysis showed that the fetus 1 had arr[19]1p36.33p36.32 (752 566 - 3 393 462)×1 and 7q35q36.3 (144 480 549 - 159 119 486)×3, and fetus 2 had arr[19]1p36.33p36.23 (752 566 - 8 362 754)×1, 6p25.3p22.3 (204 909 - 20 182 185)×3. The mother of fetus 1 had a 46,XX,t(1;7)(p36;q35) karyotype, and the mother of fetus 2 had a 46,XX,t(1;6)(p36;p22) karyotype. The karyotypes of both fathers appeared to be normal.</p><p><b>CONCLUSION</b>SNP array has the advantages such as high sensitivity and high accuracy for prenatal diagnosis, and can provide more detailed information for genetic counseling of 1p36 deletion syndrome.</p>

A Novel PCR Assay for Detecting Brucella abortus and Brucella melitensis

OBJECTIVES: Brucellosis is a major zoonotic disease that poses a significant public health threat worldwide. The classical bacteriological detection process used to identify Brucella spp. is difficult and time-consuming. This study aimed to develop a novel molecular assay for detecting brucellosis. METHODS: All complete sequences of chromosome 1 with 2.1-Mbp lengths were compared among all available Brucella sequences. A unique repeat sequence (URS) locus on chromosome 1 could differentiate Brucella abortus from Brucella melitensis. A primer set was designed to flank the unique locus. A total of 136 lymph nodes and blood samples were evaluated and classified by the URS-polymerase chain reaction (PCR) method in 2013–2014. RESULTS: Biochemical tests and bacteriophage typing as the golden standard indicated that all Brucella spp. isolates were B. melitensis biovar 1 and B. abortus biovar 3. The PCR results were the same as the bacteriological method for detecting Brucella spp. The sensitivity and specificity of the URS-PCR method make it suitable for detecting B. abortus and B. melitensis. CONCLUSION: Quick detection of B. abortus and B. melitensis can provide the most effective strategies for control of these bacteria. The advantage of this method over other presented methods is that both B. abortus and B. melitensis are detectable in a single test tube. Furthermore, this method covered 100% of all B. melitensis and B. abortus biotypes. The development of this URS-PCR method is the first step toward the development of a novel kit for the molecular identification of B. abortus and B. melitensis.

Una revisión actualizada del síndrome de deleción (monosomía) 1p36 / An updated review of 1p36 deletion (monosomy) syndrome

El síndrome de monosomía 1p36 forma parte del grupo de enfermedades conocidas como «enfermedades de baja prevalencia¼ o «enfermedades raras¼. El objetivo del presente trabajo es revisar los hallazgos de los principales estudios realizados en niños diagnosticados con el síndrome de monosomía 1p36. El fenotipo del síndrome de deleción (monosomía) 1p36 delineado desde 1997 incluye rasgos craneofaciales dismórficos: fontanela anterior grande, cejas rectas, ojos hundidos, epicanto, raíz/puente nasal anchos, hipoplasia del tercio medio facial, orejas implantadas anormalmente, filtrum largo y barbilla puntiaguda; alteraciones neurológicas: convulsiones e hidrocefalia (en casos aislados); malformaciones cerebrales observadas en imágenes por resonancia magnética (IRM): ensanchamiento ventricular, ensanchamiento de espacios subaracnoideos, alteraciones morfológicas del cuerpo calloso, entre otras. La IRM evidencia en algunos pacientes atrofia cortical, retraso en la mielinización, áreas multifocales hiperintensas, leucomalacia periventricular y heterotopia periventricular. Estos pacientes cursan con discapacidad intelectual, retrasos en el desarrollo motor, de la comunicación, del lenguaje, en el área personal-social y en la conducta adaptativa. También se observan alteraciones en el sistema auditivo, visual, cardiaco, endocrino, genitourinario, dermatológico y esquelético. Conclusiones: Existen datos de aproximadamente 100 casos en el mundo desde 1981. Esta enfermedad rara es el síndrome más común de microdeleción subtelomérica. La técnica de hibridación in situ con fluorescencia y la técnica de hibridación genómica comparativa (array-CGH) son las que mejor permiten su diagnóstico. Por el momento no existe ningún tratamiento médico efectivo para esta enfermedad.

The Monosomy 1p36 deletion syndrome is part of the group of diseases known as Rare Diseases. The objective of the present work is to review the characteristics of Monosomy 1p36 deletion syndrome. The monosomy 1p36 deletion syndrome phenotype includes: dysmorphic craniofacial features; large anterior fontanelle, unibrow, deep-set eyes, epicanthus, wide nasal root/bridge, mandible hypoplasia, abnormal location of the pinna, philtrum and pointed chin; neurological alterations: seizures and hydrocephalus (in some cases). Cerebral malformations: ventricular hypertrophy, increased subarachnoid space, morphological alterations of corpus callosum, cortical atrophy, delays in myelinisation, periventricular leukomalacia and periventricular heterotopia. These alterations produce intellectual disability and delays in motor growth, communication skills, language, social and adaptive behaviour. It is Hearing and vision impairments are also observed in subjects with this syndrome, as well as alterations of cardiac, endocrine and urinary systems and alterations at skin and skeletal level. Conclusions: Approximately 100 cases have been documented since 1981. This rare disease is the most common sub-telomeric-micro-deletion syndrome. In situ hybridization with fluorescence (FISH) and array-comparative genomic hybridization (CGH-array) are at present the two best diagnostic techniques. There is currently no effective medical treatment for this disease.

Ropinirole alters gene expression profiles in SH-SY5Y cells: a whole genome microarray study

Ropinirole (ROP) is a dopamine agonist that has been used as therapy for Parkinson's disease. In the present study, we aimed to detect whether gene expression was modulated by ROP in SH-SY5Y cells. SH-SY5Y cell lines were treated with 10 µM ROP for 2 h, after which total RNA was extracted for whole genome analysis. Gene expression profiling revealed that 113 genes were differentially expressed after ROP treatment compared with control cells. Further pathway analysis revealed modulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway, with prominent upregulation of PIK3C2B. Moreover, batches of regulated genes, including PIK3C2B, were found to be located on chromosome 1. These findings were validated by quantitative RT-PCR and Western blot analysis. Our study, therefore, revealed that ROP altered gene expression in SH-SY5Y cells, and future investigation of PIK3C2B and other loci on chromosome 1 may provide long-term implications for identifying novel target genes of Parkinson's disease.

A Rare der(Y)t(Y;1)(q12;q12) in a Patient with Essential Thrombocythemia

Among hematologic diseases, structural abnormalities of autosomal chromosomes are well-known, but cases involving the sex chromosomes are uncommon. Duplications of the long arm of chromosome 1 have been reported in several hematologic diseases including myelodysplastic syndrome, myeloproliferative neoplasms, acute myeloid leukemia, acute lymphoblastic leukemia, and Burkitt lymphoma. However, dup(1q) as a der(Y)t(Y;1)(q12;q12) is very rare. Here, we report a case of essential thrombocythemia harboring der(Y)t(Y;1)(q12;q12) with literature review.

A retrospective analysis of cytogenetic alterations in patients with newly diagnosed multiple myeloma: a single center study in Korea

BACKGROUND: The accurate identification of cytogenetic abnormalities in multiple myeloma (MM) has become more important over recent years for the development of new diagnostic and prognostic markers. In this study, we retrospectively analyzed the cytogenetic aberrations in MM cases as an initial assessment in a single institute. METHODS: We reviewed the cytogenetic results from 222 patients who were newly diagnosed with MM between January 2000 and December 2015. Chromosomal analysis was performed on cultured bone marrow samples by standard G-banding technique. At least 20 metaphase cells were analyzed for karyotyping. RESULTS: Clonal chromosome abnormalities were detected in 45.0% (100/222) of the patients. Among these results, 80 cases (80.0%) had both numerical and structural chromosome abnormalities. Overall hyperdiploidy with structural cytogenetic aberrations was the most common finding (44.0%), followed by hypodiploidy with structural aberrations (28.0%). Amplification of the long arm of chromosome 1 and -13/del(13q) were the most frequent recurrent abnormalities, and were detected in 50 patients (50.0%) and 40 patients (40.0%) with clonal abnormalities, respectively. The most common abnormality involving 14q32 was t(11;14)(q13;q32), which was observed in 19 cases. CONCLUSION: These findings demonstrate that myeloma cells exhibit complex aberrations regardless of ploidy, even from a single center in Korea. Conventional cytogenetic analysis should be included in the initial diagnostic work-up for patients suspected of having MM.

Abnormalities in Chromosomes 1q and 13 Independently Correlate With Factors of Poor Prognosis in Multiple Myeloma

BACKGROUND: We comprehensively profiled cytogenetic abnormalities in multiple myeloma (MM) and analyzed the relationship between cytogenetic abnormalities of undetermined prognostic significance and established prognostic factors. METHODS: The karyotype of 333 newly diagnosed MM cases was analyzed in association with established prognostic factors. Survival analysis was also performed. RESULTS: MM with abnormal karyotypes (41.1%) exhibited high international scoring system (ISS) stage, frequent IgA type, elevated IgG or IgA levels, elevated calcium levels, elevated creatine (Cr) levels, elevated β2-microglobulin levels, and decreased Hb levels. Structural abnormalities in chromosomes 1q, 4, and 13 were independently associated with elevated levels of IgG or IgA, calcium, and Cr, respectively. Chromosome 13 abnormalities were associated with poor prognosis and decreased overall survival. CONCLUSIONS: This is the first study to demonstrate that abnormalities in chromosomes 1q, 4, and 13 are associated with established factors for poor prognosis, irrespective of the presence of other concurrent chromosomal abnormalities. Chromosome 13 abnormalities have a prognostic impact on overall survival in association with elevated Cr levels. Frequent centromeric breakpoints appear to be related to MM pathogenesis.

Cytogenetic and molecular characterization of a patient with partial 6q trisomy and 1q monosomy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze a girl with moderate mental retardation and speech and language disorders with cytogenetics technique and next-generation sequencing (NGS).</p><p><b>METHODS</b>G-banding chromosome analysis was used to ascertain the karyotype of the child and her parents, and NGS was used for determining the size and origin of the abnormal chromosome fragment. Mate-pair and PCR were used to determine its parental origin.</p><p><b>RESULTS</b>The karyotype of the child was determined to be 46,XX,add(1)(q44)dn, while her parents were both normal. NGS revealed that the child has harbored a partial trisomy of 6q24.3-q27, and the breakpoint was mapped to at 6q24.3q27. In addition, a 2.5 Mb microdeletion at 1q44 was found in the patient.</p><p><b>CONCLUSION</b>No recognizable phenotype was associated with 1q44 deletion. The abnormal phenotypes presented by the child may be attributed to the 6q24.3-q27 triplication. Compared with conventional cytogenetic analysis, NGS has a much higher resolution and great accuracy.</p>

Genetic analysis of a fetus with partial 1q monosomy and partial 17q trisomy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze a fetus with abnormal sonographic features and correlated its genotype with phenotype.</p><p><b>METHODS</b>G-banding analysis, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed for the fetus. Karyotyping and FISH were also carried out for the parents.</p><p><b>RESULTS</b>SNP array detected a 4.4 Mb deletion at 1q44 and a 10.4 Mb duplication at 17q24.3q25.3 in the fetus. Based on the results of SNP array and FISH analysis, the father was diagnosed with a cryptic t(1;17)(q44;q24.3) translocation. The fetus has inherited a der(1)t(1;17)(q44;q24.3) from its father.</p><p><b>CONCLUSION</b>The 1q44 deletion and 17q24.3q25.3 duplication may have contributed to the abnormal sonographic features presented by the fetus.</p>

Prenatal diagnosis of 1p36.3 microdeletion in a fetus with complex heart defect / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze a fetus presenting with complex heart defect and assess the recurrence risk.</p><p><b>METHODS</b>Conventional karyotyping, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism-based array (SNP-array) were used to analyze the fetus and his parents.</p><p><b>RESULTS</b>SNP-array has detected a 6.9 Mb microdeletion at 1p36.33-p36.23 in the fetus. Chromosomal and FISH analyses indicated that the father of the fetus had a karyotype of 46,XY,t(1;14)(p36.3;p12), and that the fetus has inherited an abnormal chromosome 1 derived from the paternal translocation.</p><p><b>CONCLUSION</b>SNP-array combined with GTG banding and FISH can help to detect cryptic translocation, microdeletion or microduplication of chromosomes and is valuable to assess the recurrence risk for the affected family.</p>

Endoscopic Ultrasonography-Guided Ethanol Injection for a Pancreatic Neuroendocrine Tumor with Multiple Endocrine Neoplasia Type 1 / 대한췌담도학회지

Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder caused by mutations in the MEN1 gene on chromosome 1. Clinical diagnostic criteria for MEN1 include the presence of two or more endocrine tumors such as pituitary, parathyroid, and pancreatic islet tumors. Treatment is needed for tumors accompanied by symptoms or having malignant potential. Malignant neuroendocrine tumors (NETs) are the major cause of MEN1-related death, and pancreatic NETs account for 30-80% of MEN1 cases. Surgery is the mainstay curative treatment, and endoscopic intervention is a treatment option when patients are poor candidates for surgery. A 33-year old female patient with MEN1 was treated via endoscopic ultrasonography-guided ethanol injection for a pancreatic NET.

Endoscopic Ultrasonography-Guided Ethanol Injection for a Pancreatic Neuroendocrine Tumor with Multiple Endocrine Neoplasia Type 1 / 대한췌담도학회지

Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder caused by mutations in the MEN1 gene on chromosome 1. Clinical diagnostic criteria for MEN1 include the presence of two or more endocrine tumors such as pituitary, parathyroid, and pancreatic islet tumors. Treatment is needed for tumors accompanied by symptoms or having malignant potential. Malignant neuroendocrine tumors (NETs) are the major cause of MEN1-related death, and pancreatic NETs account for 30-80% of MEN1 cases. Surgery is the mainstay curative treatment, and endoscopic intervention is a treatment option when patients are poor candidates for surgery. A 33-year old female patient with MEN1 was treated via endoscopic ultrasonography-guided ethanol injection for a pancreatic NET.

Abnormal Karyotypes Involving 1q21 and 12p13 and Their Clinical Significance / 中国实验血液学杂志

Many hematological malignances involve recurrent chromosomal abnormalities, and the reciprocal translocation is one of them. However, there are a lot of chromosomal abnormalities with lower incidence and unclear clinical significance. Among them, the one abnormal karyotype translocation, t (1;12) (q21; p13) is a rare karyotype change. Only 6 patients had been reported to have this karyotype and all of them suffered from hematologic diseases, including one case of acute myeloid leukemia, one case of high-risk myelodysplastic syndrome, two children with acute lymphoblastic leukemia, one case of chronic myeloid leukemia at accelerated phase and one case of multiple myeloma. Among them, the fusion gene were detectable in two cases. In this article, the common chromoscme karyotype abnormality involving 1q21 and 12p13, and genes involving in these regious are summarized, moreover the reported cases of t(1;12) (q21;p13) are reviewed.

Analysis of chromosome regions 8q11.1-q13.3, 1q32-q34.3 and 14q31.1-q13.3 in a Chinese family with congenital preauricular fistula / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the candidate chromosomal region for congenital preauricular fistula (CPF) through analysis of an affected Chinese family.</p><p><b>METHODS</b>Conventional linkage analysis using short tandem repeats (STR) markers was performed to investigate three chromosomal regions 8q11.1-q13.3, 1q32-q34.3 and 14q31.1-q31.3.</p><p><b>RESULTS</b>None of 16 STRs could attain a LOD score of more than -2.0 (theta=0). Therefore, the three regions were all excluded as the candidate region for the disease.</p><p><b>CONCLUSION</b>CPF features high genetic heterogeneity. The family may have a causative gene elsewhere. Whole-genome-based study is needed to identify its genetic etiology.</p>

Application of chromosome microarray analysis for prenatal diagnosis of a fetus with partial duplication of 1p and uniparental disomy of chromosome 6 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genetic cause for a fetus with structural anomaly, and to correlate the phenotype with the genotype.</p><p><b>METHODS</b>Amniotic fluid was obtained following the revelation of structural anomaly by ultrasonography. Cell culture and direct DNA extraction were performed in parallel. G-banded karyotyping analysis and chromosome microarray analysis (CMA) were subsequently carried out.</p><p><b>RESULTS</b>G-banded karyotyping has suggested the fetus to be a normal male. However, CMA analysis has revealed the presence of a mosaic 3.24 Mb duplication of 1p36.33p36.32 (24%) and uniparental disomy (UPD) of chromosome 6. The genetic diagnosis for the fetus was therefore 46,XY, arr 1p36.33 p36.32(849,466-4,090,472)×2-3, (6)×2 hmz. The anomaly can probably explain the ultrasound findings in the fetus.</p><p><b>CONCLUSION</b>Compared with conventional cytogenetic methods, CMA has greater resolution and throughput, and can serve as a more efficient platform for the detection of chromosomal microdeletion, microduplication, loss of heterozygosity and UPD.</p>