摘要:

AbstractParangliomas of the head and neck region are usually slow growing, benign tumors. A considerable fraction has a positive family history, and the predisposing locus,PGL, has recently been assigned to 11q22‐q23. The inheritance pattern of the disease suggests thatPGLundergoes maternal genomic imprinting. We have investigated 26 tumor samples from 22 patients with head and neck paragangliomas for the occurrence of loss of heterozygosity (LOH) on all non‐acrocentric autosome arms. LOH was found only on chromosome 11, with a marked clustering on the distal half of the q‐arm. However, in many cases the resulting allelic imbalance relative to normal DNA was weak, suggesting that only part of the tumor showed this abnormality. In all eight cases where we were able to determine the parental origin, the allele undergoing loss was maternally derived. Clonality analysis with a polymorphic marker for the X‐chromosome indicated that two of three informative female cases were polyclonal, although a number of tumors carry aneuploid stemlines in DNA flow cytometry. We conclude that either tumor heterogeneity or polyclonality may explain the partial allele loss events seen in certai

ISSN:1045-2257    

DOI:10.1002/gcc.2870110202

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

年代:1994

数据来源: WILEY

摘要:

AbstractChromosome translocations involving 11q23 are associated with a number of different types of leukemia. These translocations fuse a gene encoding a putative transcription factor,HTRXI, to genes on other chromosomes. We report cloning and sequencing the t(X;II) breakpoint region from a cell line established from an infant with acute lymphocytic leukemia. The geneAFXI, on the X chromosome, is expressed in a variety of cell types. Sequence analysis indicates a high degree of homology betweenAFXIand the forkhead family of transcription factors. The high degree of identity within the forkhead region and the lack of homology outside that region suggest thatAFXIrepresents a novel forkhead family member. It is predicted that a chimeric fusion protein with altered DNA binding activity will be the result of the translocation.

ISSN:1045-2257    

DOI:10.1002/gcc.2870110203

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

年代:1994

数据来源: WILEY

摘要:

AbstractNearly all mouse plasmacytomas (MPCs) carry anIg/myctranslocation. Any one of the threelgloci may participate, while themyccontribution has been limited toc‐myc, excluding other members of themycgene family. The same is true for the other two knownlg/myctranslocation‐carrying tumors, Burkitt's lymphoma and rat immunocytoma. It is believed that thelg/mycjuxtaposition plays a decisive, rate limiting role in the genesis of the three tumors, acting through the constitutive activation ofmycthat makes it refractory to normal regulation. Here we describe the molecular analysis of a unique t(6;12)(CI;B) translocation that we previously identified in an exceptional MPC that expressedN‐mycbut notc‐myc.We now show that the translocation led to the juxtaposition ofN‐mycandlgx. This is the first case of anlg/myc‐carrying tumor that involvesN‐mycrather thanc‐myc. These findings suggest that the translocation may already have occurred at the pro‐ or pre‐B cell stage at whichN‐mycis open for transcription. According to this interpretation, constitutive activation ofN‐mycwould suppress the expression ofc‐myc, but would not interfere with the differentiation of the pro‐B cell into a fully mature plasma cell. Its tumorigenic influence would become manifest only at the time when the cell would normally be programmed to leave the cycling compartment, in connection with i

ISSN:1045-2257    

DOI:10.1002/gcc.2870110204

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

年代:1994

数据来源: WILEY

摘要:

AbstractRecently, amplification of the gene encoding a p53 binding protein, MDM2, was determined in 8% of the cases constituting a large series of glioblastomas. Here we have utilized Southern blot analysis to examine 30 cell lines established from such tumors, and our investigation has revealed large increases in MDM2 gene dosage in two cases, one of which showed coamplification of the CDK4 gene that resides in close proximity to MDM2 in chromosomal region 12q13–14. Northern analysis demonstrated overexpression of MDM2 mRNA in the two cell lines with gene amplification, and overexpression of MDM2 protein was evident in each of these by immunohistochemical and Western blot analysis. Analysis ofTP53cDNAs revealed normal TP53 sequences in the cell lines withMDM2amplification; these results are consistent with those of previous studies suggesting that MDM2 amplification occurs only in tumors expressing wild‐type p53. In total, these data suggest that MDM2 amplification in glioblastoma cell lines occurs at a frequency (6.7%) comparable to that determined in primary tumors; occurs in cell lines expressing wild‐type p53; and can involve the coamplification of additional

ISSN:1045-2257    

DOI:10.1002/gcc.2870110205

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

年代:1994

数据来源: WILEY

摘要:

AbstractChromosome rearrangements have provided useful landmarks to identify disease loci and have served as starting points for positional cloning strategies for candidate genes. We have used fluorescence in situ hybridization (FISH) and pulsed‐field gel electrophoresis (PFGE) to map three Beckwith‐Wiedemann syndrome (BWS) breakpoints and a rhabdoid tumor breakpoint more precisely. These breakpoints mapped to the interval between D11S679 and the insulin‐like growth factor 2 (IGF2) gene on 11p15.5. A cosmid (c15‐2) was identified that mapped centromeric to the BWS t(11;16) and the rhabdoid tumor‐associated t(11;22), telomeric to the BWS t(11;22), and was found to span the BWS‐associated inv(11) breakpoint. Pulsed‐field gel analysis placed all four breakpoints into a 250‐675 kb interval distal to D11S679 and at least 270 kb centromeric to the IGF2 and H19 loci. These data locate all three BWS rearrangements and the rhabdoid tumor t(11;22) breakpoint in the same region of 11p 15.5, suggesting that they may be affecting the same locus or closely linked loci. Cosmid c15‐2 provides a well‐defined starting point in the search for cand

ISSN:1045-2257    

DOI:10.1002/gcc.2870110206

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

年代:1994

数据来源: WILEY

摘要:

AbstractRecent molecular cytogenetic analysis of uterine leiomyoma cell lines with chromosome 12 aberrations has indicated that their chromosome 12 breakpoints map between linkage locus D12S8 and theCHOPgene. Here, we report fluorescence in situ hybridization (FISH) and molecular cloning studies of the chromosome 12 breakpoints in a panel of seven such uterine leiomyoma cell lines; five with the frequently observed t(12; 14)(q15;q24), one with t(12;15)(q15;q24), and one with ins(12;11)(q14;q21 qter). Directional chromosome walking studies starting from D12S8 and theCHOPgene resulted in the isolation of a relatively large number of overlapping YAC clones, including Y5355 (465 kbp), Y7673 (360 kbp), and Y9899 (275 kbp). In total, the inserts of these three YAC clones span an 800 kbp long and presumably contiguous stretch of human genomic DNA. All chromosome 12 breakpoints of the uterine leiomyoma cell lines studied were found by FISH analysis to be mapping within a 445 kbp subfragment of this region and, furthermore, to be dispersed over a DNA region which is at least 150 kbp in size. The chromosome 12 breakpoint of t(12;14)(q15;q24) in uterine leiomyoma cell line LM‐30.1/SV40 was tentatively mapped within the 60 kbp region between YAC clones Y9899 and Y5355. From this 60 kbp region and close to sequencetagged site RM99, we isolated probe pRM 118‐A, which showed in Southern blot analysis that it detected a rearrangement in LM‐30.1/SV40 DNA, and generated restriction maps of the normal and rearranged genomic DNA regions detected with this probe. Finally, we molecularly cloned part of one of those rearranged DNA fragments using a vectorette‐PCR‐based technique and demonstrated that it consisted of 12q13‐q15 sequences fused to DNA sequences derived from 14q23‐24 and most likely represented the translocation junction on der(14) in LM‐30.1/SV40 cells. Our studies strongly suggest that we have identified and isolated the uterine leiomyoma cluster region of chromosome 12 breakpoints, which we designate ULCR12, and molecularly cloned and characterized the der(14) translocation junction in cells derived from a uterine leiomyoma carrying the frequently observed t(

ISSN:1045-2257    

DOI:10.1002/gcc.2870110207

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

年代:1994

数据来源: WILEY

摘要:

AbstractAccumulation of mutations in oncogenes and tumor suppressor genes transforms a normal cell into a malignant cell by allowing it to escape from normal control of growth. In prostate tumorigenesis, the current model envisages specific mutations of theTP53tumor suppressor gene and loss of loci, detected by loss of heterozygosity (LOH), on chromosome arms 8p, 10q, 16q, and 18q. In order to determine if alterations frequently found in other adenocarcinomas (breast, ovarian, gastric, colorectal), including losses of genetic material from chromosome arms 1p, 3p, 7q, 8p, 11p, 17p, 17q, and 18q, are also involved in prostate cancer, we examined 20 localized early‐stage prostate tumors. We detected no mutations of theTP53gene. Allelic losses were found from 7q (33%), 8p (50%), 10q (20%), and 18q (33%). Furthermore, as the first step toward isolating tumor suppressor genes on 18q, we used six polymorphic markers and identified a small common deleted region between the chromosome 18 centromere and the D18S19 locu

ISSN:1045-2257    

DOI:10.1002/gcc.2870110208

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

年代:1994

数据来源: WILEY

摘要:

AbstractA pure triphasic testicular Wilms' tumor, without teratomatous elements, was studied using multiple techniques. Carcinoma in situ (CIS), the characteristic precursor of testicular germ cell tumors of adults (TGCTs), was found in the adjacent parenchyma. Flow cytometric analysis showed a single hypotriploid tumor stem line. Karyotyping of the tumor revealed some numerical and structural abnormalities, including an i(12p), the chromosomal marker of TGCTs. In situ hybridization supported the karyotypic findings, and showed a similar numerical distribution in CIS and the tumor. Molecular analysis of the tumor illustrated that all short arms of chromosome 12, including i(12p), were of maternal origin. No 12q deletions were detected. In spite of complete loss of the paternal 11p13 band, the zinc finger regions and exons 2 and 6 of the WTI gene contained no aberrations. Therefore, this tumor suppressor gene is not inactivated due to aberrations in the studied regions. In addition, all four WTI alternative transcripts were expressed in the tumor. No aberrations were found in chromosomal bands 11p15.5, 16q22.1, and 16q24. Both parental alleles of the human imprinted genesH19andIGF2were expressed in the tumor. This is the first report on the chromosomal and molecular characterization of an extrarenal Wilms' tumor. Its germ cell origin was unequivocally demonstrated.

ISSN:1045-2257    

DOI:10.1002/gcc.2870110209

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe human trithorax homolog gene (MLL) is directly involved in over 90% of cases of acute leukemia with abnormalities of 11q23. However, involvement of other genes at 11q23 both centromeric and telomeric ofMLLhas been identified in different subtypes of leukemia and lymphoma. We describe a case of acute myelomonocytic leukemia (AMML; FAB type M4) with t(10;11)(p13;q23) in which the breakpoint at 11q23 was centromeric to theMLLgene and distinct from the breakpoint seen in promyelocytic leukemias with t(11;17)(q23;q22), thus providing further evidence of heterogeneity of breakpoints in 11q23 in acute leukemia. Rearrangements of immunoglobulin (IG) and T‐cell receptor (TCR) genes were also observed, with no immunophenotypic evidence for commitment to the lymphoid lineages, indicating that inappropriate activation of the recombinases may be a feature of this particular variant translocatio

ISSN:1045-2257    

DOI:10.1002/gcc.2870110210

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

年代:1994

数据来源: WILEY

ISSN:1045-2257    

DOI:10.1002/gcc.2870110201

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

年代:1994

数据来源: WILEY