| 1. |
- Borg, Åke, et al.
(författare)
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Chromosome I alterations in breast cancer : Allelic loss on Ip and Iq Is related to lymphogenic metastases and poor prognosis
- 1992
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 5:4, s. 311-320
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Tidskriftsartikel (refereegranskat)abstract
- The development of human breast cancer is characterized by a variety of genetic alterations, and cytogenetic analyses have documented the consistent involvement of both arms of chromosome I. In the present study, molecular markers detecting restriction fragment length polymorphisms were used in pairwise screening of normal and tumor DNA to determine the frequency of allelic imbalance in breast tumors. Loss of heterozygosity (LOH) in the polymorphic epithelial mucin (PEM or MUCI) gene at 1q21 was found in 16% of 89 informative (constitutionally heterozygous) cases, whereas gain in intensity of one allelic band was more frequent (37%), a total of 47% of cases manifesting either allelic loss or gain. Three additional tumors manifested a structural alteration. Allelic loss or gain in the PEM gene was not associated with other prognostic factors, e.g., tumor size, lymph node status, steroid receptors, DNA ploidy, S phase fraction, protooncogene amplification, histological type, or patient age. However, LOH in the PEM gene was significantly correlated with early disease recurrence (P = 0.006). LOH on 1p was found in 27% of 117 informative cases, using probes for either DIS57 or DIZ2 located at 1p33‐p35 and 1p36, respectively. Somatic allelic imbalance on 1p and 1q seemed to be independent events and not the effect of loss of a whole chromosome 1. LOH on 1 p was significantly correlated to the presence of lymph node metastasis, to larger tumor size, and to DNA nondiploidy, but no correlation was found to disease outcome at this limited duration of follow‐up (median 29 months). ©1992 Wiley‐Liss, Inc.
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| 2. |
- Borrow, Julian, et al.
(författare)
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Molecular analysis of simple variant translocations in acute promyelocytic leukemia
- 1994
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 9:4, s. 234-243
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Tidskriftsartikel (refereegranskat)abstract
- The primary cytogenetic abnormality in acute promyelocytic leukemia (APL; FAB M3) is a reciprocal translocation, t(15;17)(q22;q12), which serves to fuse the PML gene on chromosome 15 to the retinoic acid receptor alpha (RARA) gene on chromosome 17. A PML-RARA fusion message transcribed from the der(15) is thought to mediate leukemogenesis. Two APL patients with simple variants of this translocation, t(3;15)(q21;q22) and t(X;15)(p11;q22), have previously been reported who lack cytogenetic involvement of chromosome 17, although their breakpoint positions on chromosome 15 still suggest the involvement of the PML gene. Here we report on a combined analysis by molecular genetics and in situ hybridization of these two patients, in which we wanted to determine whether the PML gene has alternative fusion partners or whether cryptic rearrangement of the RARA locus has occurred instead. A cryptic involvement of RARA was demonstrated in both patients by a combination of Southern analysis, reverse transcription coupled to PCR (RT-PCR), and fluorescence in situ hybridization. The results indicate an absolute requirement for the rearrangement of the RARA gene in the pathogenesis of APL and underline the importance of RARA during normal myeloid differentiation.
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| 3. |
- Panagopoulos, Ioannis, et al.
(författare)
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Fusion of the FUS gene with ERG in acute myeloid leukemia with t(16;21)(p11;q22)
- 1994
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 11:4, s. 256-262
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Tidskriftsartikel (refereegranskat)abstract
- It has been shown that the gene ERG in 21q22 is rearranged in the the t(16;21)(p11;q22) associated with acute myeloid leukemia (AML). ERG is a member of the ETS gene family and is fused with EWS in a subset of Ewing's sarcomas. EWS in 22q12 has a very high homology with FUS (also called TLS) in 16p11; the latter gene is rearranged in the t(12;16)(q13;p11) that characterizes myxoid liposarcoma. To investigate whether FUS is involved in the t(16;21) of AML, we used the Southern blot technique and polymerase chain reaction (PCR) to examine the bone marrow of a 3-year-old boy with a t(16;21)(p11;q22)-positive AML. Hybridization of Southern blot filters containing digested DNA with probes for FUS and ERG showed both germline and aberrant fragments. Using specific primers for the 5 part of FUS and the 3 part of ERG, we amplified a 4.4 kb genomic FUS/ERG DNA fragment from the leukemic sample. In a second PCR experiment, in which we used primers upstream of the 5 part of ERG and downstream of the 3 part of FUS, a 5.6 kb fragment was amplified. Blotting and hybridization with specific probes for FUS and ERG revealed that the amplified fragments consisted of FUS/ERG and ERG/FUS hybrid DNA. Both PCR fragments, when used as probes, detected germline ERG and FUS as well as aberrant fragments on Southern blot filters. The results suggest that the t(16;21) in AML leads to rearrangement and fusion of the FUS and ERG genes. This is the first example in which two genes, each known to recombine with other genes in different solid tumor types (FUS in myxoid liposarcoma and ERG in Ewing's sarcoma), are fused in a hematologic malignancy.
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| 4. |
- Pejovic, Tanja, et al.
(författare)
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Chromosome aberrations in 35 primary ovarian carcinomas
- 1992
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 4:1, s. 58-68
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Tidskriftsartikel (refereegranskat)abstract
- Cytogenetic analysis was performed on short-term cultures of primary ovarian carcinomas from 62 patients. Cytogenetic analysis was successful in 59 cases. Clonal chromosome aberrations were detected in 35 tumors. Only numerical changes or a single structural change were found in five carcinomas: trisomy 12 was the sole anomaly in two tumors, one tumor had the karyotype 50,XX, + 5, + 7, + 12, + 14, a fourth tumor had a balanced t(1;5), and the fifth tumor had an unbalanced t(8;15). The fact that four of these five carcinomas were well differentiated suggests that simple karyotypic changes are generally characteristic of these less aggressive ovarian tumors. The majority of the cytogenetically abnormal tumors (n = 30) had complex karyotypes, with both numerical and structural aberrations and often hypodiploid or near-triploid stemlines. The numerical imbalances (comparison with the nearest euploid number) were mostly losses, in order of decreasing frequency -17, -22, -13, -8, -X, and -14. The structural aberrations were mostly deletions and unbalanced translocations. Recurrent loss of genetic material affected chromosome arms 1p, 3p, 6q, and 11p. The breakpoints of the clonal structural abnormalities clustered to several chromosome bands and segments: 19p13, 11p13-15, 1q21-23, 1p36, 19q13, 3p12-13, and 6q21-23. The most consistent change (16 tumors) was a 19p + marker, and in 12 of the tumors the 19p + markers looked alike.
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| 5. |
- Åman, Pierre, et al.
(författare)
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Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11)
- 1992
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 5:4, s. 278-285
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Tidskriftsartikel (refereegranskat)abstract
- Most myxoid liposarcomas (MLS) are characterized cytogenetically by a t(12;16)(q13;p11). It is reasonable to assume that this translocation corresponds to the consistent rearrangement of one or two genes in 12q13 and/or 16p11, and that the loci thus affected are important in the normal control of fat cell differentiation and proliferation. We have used Southern blot technique to test whether a gene of the CCAAT/enhancer binding protein (C/EBP) family, CHOP, which maps to 12q13 and is assumed to be involved in adipocyte differentiation, could be the 12q gene in question. Using a cDNA probe that spans the CHOP coding region, we detected one rearranged and one wild type allele in nine of nine MLS with t(12;16). Using PCR generated, site-specific probes corresponding to the non-coding exons 1 and 2 and intron 2 of CHOP, rearrangements in five of seven tumors mapped to the 2.4 and 1.6 kbp PstI fragments that contain the first two exons and introns of the gene and the upstream promoter region. In contrast to the findings in MLS, no tumor without a t(12;16) exhibited aberrant CHOP restriction digest patterns. These tumors included one highly differentiated liposarcoma with abnormal karyotype but no involvement of 12q13, seven lipomas with various cytogenetic aberrations of 12q13-15, two uterine leiomyomas with t(12;14) (q14-15;q23-24), and one hemangiopericytoma and one chondroma, both of which also had 12q13 changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 6. |
- Axelson, H, et al.
(författare)
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Juxtaposition of N-myc and Ig kappa through a reciprocal t(6;12) translocation in a mouse plasmacytoma
- 1994
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Ingår i: Genes, Chromosomes and Cancer. - 1045-2257. ; 11:2, s. 85-90
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Tidskriftsartikel (refereegranskat)abstract
- Nearly all mouse plasmacytomas (MPCs) carry an Ig/myc translocation. Any one of the three Ig loci may participate, while the myc contribution has been limited to c-myc, excluding other members of the myc gene family. The same is true for the other two known Ig/myc translocation-carrying tumors, Burkitt's lymphoma and rat immunocytoma. It is believed that the Ig/myc juxtaposition plays a decisive, rate limiting role in the genesis of the three tumors, acting through the constitutive activation of myc that 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 expressed N-myc but not c-myc. We now show that the translocation led to the juxtaposition of N-myc and Ig kappa. This is the first case of an Ig/myc-carrying tumor that involves N-myc rather than c-myc. These findings suggest that the translocation may already have occurred at the pro- or pre-B cell stage at which N-myc is open for transcription. According to this interpretation, constitutive activation of N-myc would suppress the expression of c-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 its terminal differentiation.
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