Chromosome Aberrations ; Chromosomes, Human, Pair 13 ; Chromosomes, Human, Pair 17 ; Humans ; Multiple Myeloma ; genetics

OBJECTIVETo study the genetic basis of aberrant crypt foci (ACF), which serve as a very early morphological alteration during the development of carcinogenesis by analyzing the loss of heterozygosity (LOH).

METHODSDNA from 35 colorectal carcinomas (CRC) and 34 matched ACF were isolated by microdissection. LOH of microsatellite loci at 18q12, 18q21, 5q12, 5q21, 3p21, 2p16, 17q21, 17q11 and 11p13 was detected by means of ABI-SEQUENCER and GeneScan software was applied for analysis.

RESULTSThe rate of LOH in ACF (41.18%) was less than that in carcinoma (68.57%) (P < 0.05). The profile of LOH rates at loci 18q12, 5q12, 3p21, 17q21, 17q11, 11p13 and 2p16 in ACF was similar to that in carcinoma. The LOH frequencies on 18q12, 18q21, 5q12, 5q21, and 3p21 were higher than that on 17q11 and 11p13. However the rate at 18q21 and 5q21 in ACF was much lower than that in the carcinoma (P < 0.05). The co-existing carcinomas displayed more polypoid growth pattern and located more at the sigmoid colon and rectum. LOH in carcinomas did not correlate with the location, size, type of the carcinoma and Duke's stage.

CONCLUSIONSACF are putative preneoplastic lesions that might represent the earliest morphological lesion with the alteration at molecular genetic level. Our study provides further genetic evidence in the pathogenesis of colorectal carcinomas.

Chromosomes ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 18 ; Chromosomes, Human, Pair 2 ; Chromosomes, Human, Pair 3 ; Chromosomes, Human, Pair 5 ; Colorectal Neoplasms ; genetics ; pathology ; Humans ; Loss of Heterozygosity ; Precancerous Conditions

Adult ; Chromosome Aberrations ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 15 ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 19 ; Humans ; Leukemia, Promyelocytic, Acute ; genetics ; Male ; Translocation, Genetic

BACKGROUND: The characteristic t(15; 17) of acute promyelocytic leukemia (APL) fuses the retinoic acid receptor alpha (RARA) gene on chromosome 17 to the PML gene on chromosome 15. The test of PML-RARA rearrangement is essential for diagnosis and therapy of APL. We analyzed breakpoints of the PML gene as a basic study for PML-RARA rearrangement test. METHODS: PML-RARA rearrangements, breakpoints of the PML gene and junction sequences were analyzed in 41 patients with APL using RT-PCR and direct sequencing. RESULTS: Forty out of 41 cases revealed PML-RARA rearrangement, of which results coincided with cytogenetic data. Breakpoint distribution was 26 cases in burl (65%), one in bcr2 (2.5%), and 13 in bcr3 (32.5%). Sequencing data showed invariable joining of exon 3 of the RARA gene and exon 6 (bcrl type) or exon 3 (bcr3 type) of the PML gene. One case with bcr2 type had breakpoint in exon 6 of the PML gene with 57 bp deletion. CONCLUSIONS: Bcrl Is the most common breakpoint site of APL in Koreans, and bcy1+2/bcr3 ratio is approximately 2.1. PML-RARA junctions were continuous and joined by a correct splicing event. Breakpoint analysis would be useful in quality control of PML-RARA rearrangement test and the fused protein analysis.
Chromosomes, Human, Pair 15 ; Chromosomes, Human, Pair 17 ; Cytogenetics ; Diagnosis ; Exons ; Humans ; Leukemia, Promyelocytic, Acute* ; Quality Control ; Receptors, Retinoic Acid

Objective: To evaluate the prognostic significance of combining ISS-Ⅲ and high risk cytogenetic abnormalities [HRCAs, including 1q gain/amplification and del (17p) ] in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: The clinical characteristics and relevant variables were retrospectively analyzed in a total of 270 NDMM patients diagnosed between November 2009 and May 2018. ISS-Ⅲ stage and HRCAs [detected by FISH, including 1q gain/amplification and del (17p) ] were defined as risk factors (hit) . Based to the number of hit per case, these patients were divided into four groups carrying 0 to 3 risk factors, respectively. Progress-free survival (PFS) and overall survival (OS) were then analyzed using the Kaplan-Meier estimator. Results: Patients who carried single hit (n=120, 44.4%) had shorter median PFS (23.0 vs 28.9 months; P>0.05) and OS (42.3 vs 53.7 months; P>0.05) than those with no risk factors (n=66, 24.4%) . Of note, the outcome of patients who had two or more risk factors (double/triple, n=84, 31.1%) was much worse than those with either no or one risk factor, indicated by significantly reduced median PFS (14.5 months; HR=1.584, 95%CI 1.082-2.319; P=0.003 for double/triple vs single hit) and OS (18.4 months, HR=2.299, 95%CI 1.485-3.560; P<0.001 for double/triple vs single hit) . Strikingly, patients who had three risk factor (triple hit, n=5, 1.9%) displayed the poorest survival with extraordinarily shorter PFS (0.9-15.1 months) and OS (0.9-18.9 months) compared to those carrying two risk factors (double hit) . Analogous results were obtained when different combinations of ISS stages and HRCAs were analyzed. Conclusion: These results suggest a potential but rather important role of combining multiple (e.g. double or triple) adverse factors determined via the routine ISS staging and FISH detection of cytogenetic abnormalities in risk stratification and prognostic prediction, which might be helpful to identify high risk patients more precisely at diagnosis. It also raised a possibility that a small group of ISS-Ⅲ patients carrying both 1q gain/amplification and del (17p) might represent an "extremely-high risk" subset of MM.
Chromosome Aberrations ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 17 ; Humans ; Multiple Myeloma ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Analysis

Recently, thanks to the development of the molecular genetics which had made us understand the nature of some genetic disorders, the concept of the classification has changed. Charcoal-Marie-Tooth disease (CMT) is the most conspicuous disease. The disease is inherited as an autosomal dominant trait. CMT is classified into two major forms: demyelinating CMT type 1 and axonal CMT type 2. CMT type 1 loci are known to map to chromosome 17 (CMT IA), chromosome 1 (CMT IB), X chromosome (CMT IX), and unknown autosome (CMT IC). And CMT type 2 loci are divided into chromosome 1 (CMT 2A) and chromosome 3 (CMT 2B). The most prevalent form is CMT IA caused by a duplication in a region of chromosome 17p11.2-12. Peripheral myelin protein-22 (PMP-22) gene In that region is known to being responsible for the disease. In Korea, although several families of CMT were reported, there is no report on the subtype of CMT type 1 confirmed by genetic analysis. We report a family of CMT IA confirmed by molecular genetic analysis using D17s122 markers.
Axons ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 3 ; Classification ; Humans ; Korea ; Molecular Biology* ; Myelin Sheath ; X Chromosome

Recently, thanks to the development of the molecular genetics which had made us understand the nature of some genetic disorders, the concept of the classification has changed. Charcoal-Marie-Tooth disease (CMT) is the most conspicuous disease. The disease is inherited as an autosomal dominant trait. CMT is classified into two major forms: demyelinating CMT type 1 and axonal CMT type 2. CMT type 1 loci are known to map to chromosome 17 (CMT IA), chromosome 1 (CMT IB), X chromosome (CMT IX), and unknown autosome (CMT IC). And CMT type 2 loci are divided into chromosome 1 (CMT 2A) and chromosome 3 (CMT 2B). The most prevalent form is CMT IA caused by a duplication in a region of chromosome 17p11.2-12. Peripheral myelin protein-22 (PMP-22) gene In that region is known to being responsible for the disease. In Korea, although several families of CMT were reported, there is no report on the subtype of CMT type 1 confirmed by genetic analysis. We report a family of CMT IA confirmed by molecular genetic analysis using D17s122 markers.
Axons ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 3 ; Classification ; Humans ; Korea ; Molecular Biology* ; Myelin Sheath ; X Chromosome

OBJECTIVETo investigate the common chromosome abnormalities of the patients with multiple myeloma in China and the relationships of cytogenetic abnormalities and clinical features.

METHODSIn interphase fluorescence in-situ hybridization (FISH) analysis, a panel of probes including D13S319 (13q14.3), RB1(RB1 gene), IgH (14q32), P53(17p13), 1q21(1q21 gene) was used to study the cytogenetic abnormalities of 31 patients with multiple myeloma; and the clinical implications of cytogenetic abnormalities were investigated.

RESULTThe frequencies of the partial deletion of chromosome 13, translocation involving the 14q32 region, abnormalities in 1q21 and deletion of 17p13 were 45%, 68%, 50%, and 35% in the study, respectively. The abnormalities of both the partial deletion of chromosome 13 and translocation involving the 14q32 region were found in 35% of the patients. 79% of the patients with del (13q) had 14q32 translocations simultaneously. All the patients with positive detection of probe D13S319 were found to have translocation of 14q32 at the same time. There were correlations between the partial deletion of chromosome 13 and translocation involving the 14q32 region. The overall response rate of induction treatment was 67.7%. No significant difference was found in patients with positive or negative cytogenetic abnormalities of del(13q), 14q32 translocation, del(17p13), and 1q21 abnormalities.

CONCLUSION13q deletion, IgH rearrangement, chromosome 1 abnormality and 17p13 deletion are the common cytogenetic abnormalities of MM patients in China. There is a significant correlation between the presence of 14q32 translocations and chromosome 13 deletion in MM patients.

Adult ; Aged ; Chromosome Deletion ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 13 ; Chromosomes, Human, Pair 14 ; Chromosomes, Human, Pair 17 ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Multiple Myeloma ; genetics ; Translocation, Genetic

OBJECTIVETo investigate global genetic alterations in medulloblastoma, and to localize critical chromosomal loci with allelic imbalances associated with the development of medulloblastoma.

METHODSA high-resolution genome-wide allelotype analysis, including 384 microsatellite markers, was performed in 12 medulloblastomas.

RESULTSAn average of 238 (62.3%) allelic imbalances were detected on all 39 autosomal arms. Non-random allelic gains or losses were detected on chromosomes 7q (58.3%), 8p (66.7%), 16q (58.3%), 17p (58.3%) and 17q (66.7%). In addition, chromosomal arms with frequencies of allelic imbalances higher than the mean percentage were identified on 3p (33.3%), 3q (33.3%), 4q (41.7%), 7p (33.3%), 8q (41.7%), 10q (41.7%), 13q (33.3%), 14q (33.3%) and 20q (33.3%). No relationship was found between the frequency of allelic imbalances and the clinical outcome of the patients.

CONCLUSIONSA global view of the genetic alterations in medulloblastoma was provided. The allelic imbalances involving chromosomes 7q, 8p, 16q, 17p and 17q may play an important role in the pathogenesis of medulloblastoma.

Adolescent ; Adult ; Alleles ; Allelic Imbalance ; Cerebellar Neoplasms ; genetics ; Child ; Child, Preschool ; Chromosomes, Human, Pair 16 ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 7 ; Chromosomes, Human, Pair 8 ; Female ; Genotype ; Humans ; Male ; Medulloblastoma ; genetics ; Microsatellite Repeats ; genetics

OBJECTIVETo explore the value of fluorescence in situ hybridization (FISH) and multiplex fluorescence in situ hybridization (M-FISH) techniques in the detection of genetic changes in chronic myeloid leukemia (CML) with variant Philadelphia translocation (vPh).

METHODSCytogenetic preparations from 10 CML patients with vPh confirmed by R banding were assayed with dual color dual fusion FISH technique. If only one fusion signal was detected in interphase cells, metaphase cells were observed to determine if there were derivative chromosome 9[der (9)] deletions. Meanwhile, the same cytogenetic preparations were assayed with M-FISH technique.

RESULTSOf the 10 CML patients with vPh, 5 were detected with der (9) deletions by FISH technique. M-FISH technique revealed that besides the chromosome 22, chromosomes 1, 3, 5, 6, 8, 10, 11 and 17 were also involved in the vPh. M-FISH technique also detected the abnormalities which were not found with conventional cytogenetics (CC), including two never reported abnormalities.

CONCLUSIONThe combination of CC, FISH and M-FISH technique could refine the genetic diagnosis of CML with vPh.

Adult ; Aged ; Chromosomes, Human, Pair 1 ; genetics ; Chromosomes, Human, Pair 10 ; genetics ; Chromosomes, Human, Pair 11 ; genetics ; Chromosomes, Human, Pair 17 ; genetics ; Chromosomes, Human, Pair 22 ; genetics ; Chromosomes, Human, Pair 3 ; genetics ; Chromosomes, Human, Pair 5 ; genetics ; Chromosomes, Human, Pair 6 ; genetics ; Chromosomes, Human, Pair 8 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Karyotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; genetics ; Male ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; Translocation, Genetic ; genetics ; Young Adult