摘要:

AbstractIncreased dosage of cellular oncogenes resulting from amplification of DNA is a frequent genetic abnormality of tumor cells and the study of oncogene amplification has been paradigmatic for the usefulness of molecular genetic research in clinical oncology. Certain types of human tumors carry an amplified cellular oncogene at frequencies of up to 50–60%. Human neuroblastoma has been prototypic for the importance of oncogene amplification in tumorigenesis, and evidence is emerging that amplification may be an early event involved in a more malignant form of this cancer. It is unclear at which stage amplification plays a role in other cancers. Amplification of cellular oncogenes is a good predictor of clinical outcome in some human malignancie

ISSN:1045-2257    

DOI:10.1002/gcc.2870010302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractMolecular study of a t(1;14)(p32;q11) translocation found in an acute T‐cell leukemia (Kd cells) with a relatively mature phenotype is reported. Complex DNA rearrangements were characterized in theTCRα/δ locus. Besides a productive Vα/Jα assembly found on the normal allele, two deletions within the Jα cluster were identified in the translocated allele. The translocation breakpoints involved theTCRα gene on chromosome 14 and theSCLlocus on chromosome band 1p32 that was recently shown to be activated by the t(1;14) translocation of the DU 528 leukemic cell line. Significantly, both Kd and DU 528 translocation breakpoints were located at the boundaries of Dδ or Jδ segments and were clustered in a 10 kb genomic fragment of theSCLgene. The presence of recombination signal motifs (heptamer‐12/23 bp spacer‐nonamer) on both normal chromosome partners, and N nucleotide addition on both derivative chromosomes involved the recombinase system in the translocation event. TheSCLlocus was highly expressed as a 5 kb transcript in Kd cells and, as already reported, as a 2 kb transcript in DU 528 cells. Importantly, a 5 kbSCLtranscript was also detected in immature nonlymphoid hematopoietic cells but not in normal mature T cells, suggesting that it might correspond to the normalSCLtranscript. Taken together, our data support the notion that the involvement of theSCLgene in the leukemogenic process may occur through overexpression of an apparently normal transcript (Kd cells) or expression of a truncated RNA (

ISSN:1045-2257    

DOI:10.1002/gcc.2870010303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractShort‐term cultures from 12 oral squamous cell carcinomas were cytogenetically investigated. A normal karyotype was found in 3 tumors, 2 of which had many nonclonal changes. Clonal chromosome abnormalities were detected in the remaining 9 cases, in 6 of them in the form of 2 or 3 abnormal clones. In 5 cases the different clones were cytogenetically unrelated, suggesting a multiclonal origin. Numerous additional nonclonal changes were present in 4 of the 9 tumors with clonal aberrations. None of the structural aberrations, clonal or nonclonal, were found in more than one case; nor did any of the rearrangements correspond to cancer‐associated aberrations known from other tumors. The aberration breakpoints of the present series and of a previously reported tongue cancer clustered to bands 1p32, 1p22, 1p11, 1q21, 1q23, 1q25, 1q32, 1q42, 1q44, 2q31, 3p11, 4q35, 7p22, 11p15, 11q13, 12q24, and 17

ISSN:1045-2257    

DOI:10.1002/gcc.2870010304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractEvidence for gene dosage effect for β‐glucuronidase (GUSB) and phosphoserine phosphatase (PSP), whose genes are mapped on chromosome 7, was searched in a group of 13 patients with myeloproliferative disorders and acquired monosomy 7. The monosomy 7 was the sole anomaly in nine patients and was associated with other chromosome changes in four. A group of 19 patients with similar diseases but with normal karyotype or with anomalies not involving chromosome 7 served as control. β‐galactosidase and arylsulphatase A, whose genes are not on chromosome 7, were tested as control enzymes. We obtained evidence for a gene dosage effect for GUSB, but not for PSP. When all cases with monosomy 7 were compared with controls, no dosage effect was observed for PSP, but when this group was split into two, according to the presence of anomalies additional to the monosomy 7, the values of activity in the group with additional anomalies were significantly lower than in the controls. Thus, in the case of PSP, the loss of one allele is not followed immediately by reduction in activity, and this could be due to the specific importance of PSP in nucleic acid metabolism. We postulate that some regulatory mechanisms are able to keep normal levels of PSP even in the presence of only one allele, and that they are overwhelmed only when additional chromosome changes are present. These changes tend to involve chromosomes carrying genes for enzymes involved in a metabolic pathway closely related to PSP functions, and only then is a gene dosage effect for PSP detec

ISSN:1045-2257    

DOI:10.1002/gcc.2870010305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractThe cytogenetic study of a series of 79 colorectal cancers was performed with special attention to sex chromosome behavior. It was found that apart from other chromosomal changes, the early‐replicating X chromosome (Xe) was frequently duplicated in tumors from both males and females. This contrasted with a frequent loss of either the late‐replicating X (XI) in tumors from females or of the Y chromosome in tumors from males. All the detected unbalanced rearrangements resulted in a gain of the long, but not the short, arm of the X chromosome. The replication pattern of Xe chromosomes was similar to that of control tissues, whereas that of XI chromosomes was unusual. Its main characteristic was that the two major R bands of the short arm, Xp11 and Xp22, replicated too ea

ISSN:1045-2257    

DOI:10.1002/gcc.2870010306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractWe have studied 31 male germ cell tumors (GCTs) for probable mutations in codons 12, 13, and 61 ofHRAS, KRAS, andNRASoncogenes using the polymerase chain reaction. Twenty of the thirty‐one tumors exhibitedNRASgene mutations, 14 in codon 61, and six in codon 12, whereas no mutations were detected inHRASandKRASgenes. TheNRASmutations were equally prevalent in seminomatous and nonseminomatous GCTs. Thus 13 of 22 seminomas, six of seven embryonal carcinomas, and one of two mixed tumors exhibited mutations. Two non‐seminomatous tumors (an embryonal carcinoma and a yolk sac/teratoma) had mutations in both codons 12 and 61. The high frequency ofNRASmutations observed in the present study suggests that NRAS gene products may play an important role in growth regulatory functions of premalignant and malignant germ ce

ISSN:1045-2257    

DOI:10.1002/gcc.2870010307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractWe have previously described a patient in whom the breakpoint occurred within the first intron of theBCRgene and have cloned the 9q+ and 22q− junctions. We have now determined the nucleotide sequence around the breakpoints on both translocation products from this patient as well as the corresponding regions from the normal chromosomes 9 and 22. We have compared the sequence with that of the breakpoint regions in the Ph1‐positive leukemic patients in order to check for the presence of conserved motifs. A + T‐rich sequences and ALU repeat elements are the only sequence characteristics which appear to be very common around translocation regions. The chromosome 9ABLsequences at or adjacent to the breakpoints present in the 22q‐ product show homology to the consensus ALU sequence while the chromosome 22 sequences do not, suggesting a non‐homologous recombination mechanism. While no sequences are deleted, there is a two‐base‐pair “homology” at the junction. Therefore, staggered breaks followed by ligation and repair could be part of the mechanism involved in the process of translocation in some cases of

ISSN:1045-2257    

DOI:10.1002/gcc.2870010308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractWe used 10 restriction fragment length polymorphism (RFLP) probes spanning the length of the short arm of chromosome 3 (3p) to map deletion sites in human lung cancer. Two approaches were used. 1) When a patient's tumor and normal tissue were available, loci with allelic heterozygosity in the normal tissue were tested for loss of alleles at 3p. 2) When the corresponding normal tissue was not available, the frequency of heterozygosity at each locus in a panel of tumors was compared to the corresponding published frequencies in nontumor tissue of healthy individuals or patients with lung cancer. In 14 small cell lung carcinomas (SCLC) with normal DNA for comparison, allele loss was found at all heterozygous loci, with one exception at a locus near the 3p centromere (D3S4). In the total of 53 SCLCs, which included tumors without paired normal tissue, frequency of heterozygosity was significantly reduced in all 10 3p loci. Three loci, DNF15S2,RAF1, and D3S18, were homozygous in all tumors in the SCLC panel. These loci, which are in regions 3p21 and 3p25, may thus be involved in the origin or evolution of SCLC. We also investigated 24 non‐SCLC tumors. In this panel, frequency of heterozygosity was significantly reduced at seven of the 10 loci tested. Comparison of the results shows that the pattern of allele loss on 3p is different in SCLC and non‐SCLC, suggesting a difference in pathogenesis at the genetic le

ISSN:1045-2257    

DOI:10.1002/gcc.2870010309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

摘要:

AbstractThe t(14;19)(q32.3;q13.1) is a recurring translocation found in the neoplastic cells of some patients with chronic lymphocytic leukemia (CLL). We have previously cloned the translocation breakpoint junction present in the leukemic cells from one such patient. In the present study, we have cloned and sequenced the breakpoint junction from a second patient. The breakpoint on chromosome 14 occurs within a switch region upstream of the immunoglobulin heavy chain Cα1 sequence. We detected a 2.1–2.3 kb transcript on Northern blots using a probe from chromosome 19 adjacent to this breakpoint. S1nuclease protection experiments showed that transcription of the gene proceeds in a direction away from the breakpoint junction. This gene (for which we propose the nameBCL3) may contribute to the malignant development of B‐lymphocytes following the chromosome translocation. If so, it is the first protooncogene identified whose activation is principally associated with

ISSN:1045-2257    

DOI:10.1002/gcc.2870010310

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY

ISSN:1045-2257    

DOI:10.1002/gcc.2870010301

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1990

数据来源: WILEY