Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protein kinase, interferon-inducible double-stranded (ds)RNA-dependent activator (PRKRA) is a dsRNA-binding protein which activates a protein kinase participating in the antiviral activity of interferon. Our previous studies indicated that the nucleotide sequence encoding PRKRA, which appeared to be an intronless gene, was present in PAC HS265J14 containing the human leukocyte antigen (HLA) DR subregion. In this study, we further investigated and characterized the PRKRA gene on the human genome by means of Southern blotting and polymerase chain reaction with homozygous typing cell lines for HLA genes. Results indicated that the presence of PRKRA in the DR subregion was dependent on the DR53 group. Consistently, fluorescence in situ hybridization profiles with PRKRA as a probe showed that the hybridization signal on Chromosome (Chr) 6p21.3 was seen only in the samples carrying the DR haplotypes that belonged to the DR53 group. Interestingly, another hybridization signal, which was mapped on Chr 2q31.2-q32.1, was always detected in the samples examined, i.e., even in the samples negative for the DR53 group. The outcome of a sequence-database homology search further indicated that the PRKRA gene with introns appeared to be present in a recently opened draft-sequence, RP11-65L3 (GenBank accession number AC009948), which is located between D2S335 and D2S2257. Together, the data presented here indicate that the PRKRA gene in the DR subregion is a processed pseudogene (PRKRApsi), which could have been generated only on the DR53 common ancestor's genome, and that the master copy of PRKRApsi is most probably present on Chr 2q31.2-q32.1.
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PMID:Haplotype-specific sequence encoding the protein kinase, interferon-inducible double-stranded RNA-dependent activator in the human leukocyte antigen class II region. 1122 Jun 20

Recently, we reported that a recurrent translocation, t(1;3)(p36;p21) is closely associated with prior chemotherapy including alkylating agents, assessing eight patients with various hematologic malignancies (Genes, Chromosomes and Cancer 34:186-192), 2002). Furthermore, we delineated the 1p36 breakpoint in two patients lying between RP11-BAC47P3 and RP5-PAC963K15 at 1p36.3 with a small deletion near the breakpoint. In one of them, we also found deletion at 3p21.3 with cosNRL9 probe, which is included in a 370-kb lung cancer homologous deletion region. However, due to scantiness of the patient materials at that time, we could not determine the precise breakpoint at 1p36 or 3p21 in any of the patients. In this report, we identified the 1p36 and 3p21 breakpoints of an AML (M3) patient who is included in the previous patient series. The patient showed t(1;3)(p36;p21) together with t(15;17) at the third relapse. With FISH using BAC/PAC probes, we determined the 1p36 breakpoint within RP11-295B1 at 1p36.2 and the 3p21 breakpoint between RP11-3B7 and RP11-901L6 at 3p21.3. There was no deletion around the two breakpoints in this patient. To the best of our knowledge, this is the first report that has identified the precise breakpoint of t(1;3)(p36;p21) translocation. It is obvious that the 1p36.2 and 3p21.3 breakpoints of this patient are different from those of the previous patients, suggesting that the genes and the molecular event is different from those of the previous patients. The patients with t(1;3)(p36;p21) should be subclassified according to the precise breakpoints or the genes involved.
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PMID:Identification of the breakpoints at 1p36.2 and 3p21.3 in an AML(M3) patient who had t(1;3)(p36.2;p21.3) at the third relapse. 1237 31

In neuroblastoma, the most frequent genetic alteration is gain of chromosome arm 17q, which arises from unbalanced translocations. To document these genetic events more precisely, we performed an extensive study of chromosome 17 breakpoints in 27 neuroblastoma cell lines by using a combination of fluorescence in situ hybridization mapping with BAC/PAC clones and allele analysis with polymorphic markers. All cases exhibited one or more unbalanced chromosome 17 translocations, and 15 distinct breakpoint regions could be mapped. This high variability indicates that gene fusion or disruption events are extremely unlikely to account for the underlying oncogenic role of these translocations. However, breakpoints were not randomly distributed, most of them mapping to the proximal part of 17q. As a result of translocations, all cell lines but one exhibited gain of the 53.5 Mb-->qter fragment, bordered proximally by the clone CTC-462L7. The most telomeric breakpoint, flanked by the clone RP11-443M10, defined the 70.9 Mb-->qter fragment as a region of additional gain. In addition to chromosome gains, loss of heterozygosity for the short arm of chromosome 17 was observed in close to half the cases. It was either related to a chromosome 17 monosomy or to a uniparental isodisomy. Finally, in cases with a single normal chromosome 17, we show that the parental origin of the translocated chromosome 17 can be either distinct or identical to that of the normal chromosome. Similarly, multiple translocations within the same cell line can either involve the same or different chromosome 17 homologues, indicating the likely absence of parental origin bias in the generation of these alterations.
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PMID:Variety and complexity of chromosome 17 translocations in neuroblastoma. 1469 94

Hemophilia B is an X-linked bleeding disorder caused by the deficiency of coagulation factor (F)IX, with an estimated prevalence of 1 in 30 000 male births. It is almost exclusively seen in males with rare exceptions. We report a girl who was diagnosed with severe (<1%) FIX deficiency at 4 months of age. Cytogenetic studies in the patient showed a balanced translocation between one of the X-chromosomes and chromosome 14, with breakpoints at bands Xq27.1 and 14q32.3. Both parents were found to have normal chromosomes. Late replication studies by incorporation of 5-bromodeoxyuridine showed non-random inactivation of the normal X-chromosome, a phenomenon frequently seen in balanced X/autosome translocations. To map the breakpoint, fluorescent in-situ hybridization was performed. A PAC DNA probe, RP6-88D7 (which contains the FIX gene) hybridized only on the normal chromosome X as well as onto the derivative 14. Using a PAC DNA probe, RP11-963P9 that is located proximal to the FIX gene, we obtained signals on the normal and derivative X and also on the derivative 14. We conclude that the breakpoint is located within the DNA sequence of this clone mapping proximal to the FIX gene. Since the FIX gene seems to be intact in the derivative 14, the breakpoint may affect an upstream regulatory sequence that subjects the gene to position effect variegation (PEV).
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PMID:Breakpoint of a balanced translocation (X:14) (q27.1;q32.3) in a girl with severe hemophilia B maps proximal to the factor IX gene. 1500 60

Chromosome abnormalities of 6q are not frequently observed in myeloid disorders. In this article, we report the incidence of these chromosome changes in childhood myeloid leukemia as 2%-4% based on the cytogenetic database of a single institution. We applied fluorescence in situ hybridization (FISH) to characterize precisely the types of 6q abnormalities in seven patients (six with acute myeloid leukemia and one with myelodysplastic syndrome). They carried various translocations involving different breakpoints in 6q, as confirmed by FISH using a whole-chromosome-6 paint. Four cases were reported as t(6;11), although the breakpoints varied. Among these, we identified a novel translocation, t(6;11)(q24.1;p15.5), in a patient with acute megakaryoblastic leukemia. Molecular cytogenetic studies using the PAC clone RP5-1173K1 localized the genomic breakpoint on chromosome 11 to within the NUP98 gene. The breakpoint on chromosome 6 was narrowed down to a 500-kb region between BAC clones RP11-721P14 and RP11-39H10. Reverse-transcription PCR was performed using a forward primer specific for NUP98 and a reverse primer for the candidate gene in the 500-kb interval in 6q. This experiment resulted in the identification of a new fusion between NUP98 and C6orf80. Further studies will aim to fully characterize C6orf80 and will elucidate the role of this new NUP98 fusion in myeloid leukemia.
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PMID:Characterization of 6q abnormalities in childhood acute myeloid leukemia and identification of a novel t(6;11)(q24.1;p15.5) resulting in a NUP98-C6orf80 fusion in a case of acute megakaryoblastic leukemia. 1602 18

Early (T1 stage) adenocarcinoma of the esophagus or gastroesophageal junction is a potentially curable disease. We analyzed the genomic spectra of 33 early neoplastic lesions after subdividing the tumors into six depths of invasion (T1-mucosal, m1-m3; T1-submucosal, sm1-sm3). Two subgroups were defined, T1m1-sm1 (n = 18) and T1sm2-sm3 (n = 15). The latter group is associated with frequent lymphatic spread and a high percentage of local and/or distant recurrence. Comparative genomic hybridization with a genomewide 3,500-element BAC-PAC array revealed a characteristic gastroesophageal adenocarcinoma pattern of changes, with losses on chromosome arms 4pq, 5q, 8p, 9p, 17p, and 18q and gains on 1q, 6p, 7pq, 11q, 15q, 17q, and 20pq. However, when the two groups were compared, the following BAC clones showed significantly more alterations in the T1sm2-sm3 group: RP11-534L20 (1q32.1) and RP11-175A4 (6p21.32), showing gains, and RP11-356F24, RP11-433L7, and RP11-241P12 (all at 8p), showing losses. Gain of RP11-534L20 (1q32.1) and loss of RP11-433L7 (8p22) were associated not only with a recurrence-free period (P = 0.0007 and 0.007, respectively), but also with regional lymphatic dissemination (P = 0.005 and 0.003, respectively). These DNA clones can be considered genomic markers for the aggressive behavior of early esophageal and gastroesophageal junction adenocarcinoma.
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PMID:Genomic analysis of early adenocarcinoma of the esophagus or gastroesophageal junction: tumor progression is associated with alteration of 1q and 8p sequences. 1647 70

Fluorescence in situ hybridization (FISH) analyses were performed on six of seven patients who had been reported in 2004 to have an i(20q-) anomaly expressed as ider(20)(q10)del(20)(q11q13). The i(20q-) was investigated with a series of probes: a centromere-specific probe for chromosome 20, two paint probes for 20p and 20q, and a panel of locus-specific probes prepared from BAC/PAC clones mapped to 20p. The results showed that: (1) i(20q-) was a dicentric chromosome; (2) both of its arms comprised a deleted 20q and a small part of 20p near the centromere of chromosome 20; and (3) the breakpoints and reunion sites of i(20q-) differed, residing in the region 20p11.21-20p11.22 delineated by BAC/PAC clones RP11-96L6 and RP13-401N8. Thus, i(20q-) could be more precisely described as a der(20)del(20)(q11q13)idic(20)(p11).
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PMID:FISH studies identify the i(20q-) anomaly as a der(20)del(20)(q11q13)idic(20)(p11). 1650 89

We report on a 6-year-old girl who presented at 6 months of age with seizures, delayed psychomotor development and mild facial dysmorphism. A small muscular ventricular septal defect was documented on echocardiogram and brain MRI showed a frontal brain anomaly. Urine organic acid analysis revealed dicarboxylic aciduria, and plasma acylcarnitine analysis showed marked elevation of octanoyl (C8) and decanoyl (C10) carnitines with C8:C10 ratio of 9:1. These results were indicative of medium chain acyl-CoA dehydrogenase deficiency. ACADM gene sequencing showed an apparent homozygous c.166G > C (Ala31Pro) missense mutation in exon 3; however, only the mother was found to be a carrier of this novel missense mutation. This finding along with non-regressive developmental delay prompted further karyotype and genomic investigations. An interstitial deletion of chromosome 1 was detected by repeat G-banding: 46,XX,del(1)(p22.2p31.1). Parental karyotypes were normal. The deletion was characterized by array CGH analysis using a 1 Mb BAC/PAC array platform. Clones deleted extended from RP11-88B10 (1p31.1) to RP5-1007M22 (1p22.2), a 15.5 Mb deletion which includes the ACADM locus. Clinical review of 6/7 cases of interstitial deletions with breakpoints of 1p22 and 1p31/32, including the patient in this report, indicate a variable phenotype. Thus, although G-band breakpoints are similar, common breakpoints for these alterations are unlikely. This is the first report of a patient with fatty acid oxidation defect caused by a mutation in combination with an interstitial chromosomal deletion.
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PMID:Interstitial deletion of 1p22.2p31.1 and medium-chain acyl-CoA dehydrogenase deficiency in a patient with global developmental delay. 1847 88