- Email: [email protected]
A chronic myelocytic leukemia case bearing deletions on the three chromosomes involved in a variant t(9;22;11)
Cancer Genetics and Cytogenetics 148 (2004) 137–140
Short communication
A chronic myelocytic leukemia case bearing deletions on the three chromosomes involved in a variant t(9;22;11) Luisa Anellia,b, Francesco Albanoc, Antonella Zagariaa,c, Arcangelo Lisoc, Maria Grazia Robertib, Mariano Rocchia, Giorgina Specchiab,c,* a
Sezione di Genetica, Dipartimento di Anatomia Patologica e Genetica, University of Bari, Bari, Italy b Department of Hematology, University and Hospital of Foggia, Foggia, Italy c Department of Hematology, University of Bari, Policlinico, Piazza G. Cesare 11, 70124 Bari, Italy Received 21 April 2003; received in revised form 27 May 2003; accepted 30 May 2003
Abstract
Genomic deletions on the derivative chromosomes bearing the reciprocal fusion gene have recently been reported in chronic myelocytic leukemia (CML). We here describe a CML case with a variant rearrangement t(9;22;11)(q34;q11;q13) showing the loss of chromosome 11 sequences in addition to der(9) deletions. Known tumor suppressor genes involved in apoptosis and in the control of cell proliferation were found to be mapped to the lost sequences. Our findings indicate that genomic deletions may occur also on the third derivative chromosome in variant t(9;22). 쑖 2004 Elsevier Inc. All rights reserved.
1. Introduction
2. Materials and methods
Approximately 90%–95% of chronic myelocytic leukemia (CML) cases are characterized by the Philadelphia chromosome (Ph), which arises from the reciprocal t(9;22)(q34;q11). About 5%–10% of CML patients show a variant translocation, involving one or more chromosomes in addition to 9 and 22. Three-, four-, and five-way variant translocations have been reported [1]. In the majority of variant translocations, the Ph chromosome is cytogenetically detectable, but in rare cases it is masked in the form of additional material transposed on the derivative chromosome 22 [2]. Genomic deletions on the derivative chromosomes bearing the reciprocal fusion gene have recently been observed in CML [3]. In a previous article, we reported three CML cases with complex variant translocations, showing deletions on the third chromosome, in addition to deletions of chromosomes 9 and 22 sequences [4]. We describe a new CML case with a three-way variant rearrangement, carrying genomic deletions on the third chromosome involved in the translocation in addition to deletions on der(9).
2.1. Cytogenetic analysis Conventional cytogenetic analysis of a 24- to 48-hour culture was performed on bone marrow cells at diagnosis with standard techniques and evaluated with Giemsa–trypsin–Giemsa banding at about the 400-band level according to International System for Human Cytogenetic Nomenclature (ISCN 1995) [5]. Twenty-five metaphases were scored. 2.2. FISH studies Fluorescence in situ hybridization (FISH) experiments were performed at diagnosis on bone marrow samples. Chromosome preparations were hybridized in situ with probes labeled with Cy3 and FluorX (Amersham, Piscataway, NJ) by nick translation. Digital images were obtained using a Leica DMRXA epifluorescence microscope equipped with a cooled charge-coupled device camera. Cy3 (red), FluorX (green), and 4′,6-diamidino-2-phenylindole (DAPI; blue) fluorescence signals, detected using specific filters, were recorded separately as gray-scale images. Pseudocoloring and merging of images were performed using Adobe Photoshop software. 2.3. Whole chromosome paint (WCP) and probes
* Corresponding author. Tel.: +39-80-5478711; fax ⫹39-80-5428978. E-mail address: [email protected] (G. Specchia). 0165-4608/04/$ – see front matter 쑖 2004 Elsevier Inc. All rights reserved. doi:10.1016/S0165-4608(03)00246-2
WCPs for chromosomes 9, 11, and 22, obtained from flow-sorted chromosomes, were supplied by the Wellcome
138
L. Anelli et al. / Cancer Genetics and Cytogenetics 148 (2004) 137–140
Trust Sanger Institute, Hinxton, UK. The ABL1 gene was identified by using a pool of the two overlapping P1-derived artificial chromosomes (PACs) dJ835J22 and dJ1132H12; bacterial artificial chromosome (BAC) bA164N13 encompasses the major breakpoint region of the BCR gene [6]. To identify all the breakpoints, we used 15 probes proximal to ABL1, 11 clones distal to BCR, and 12 probes for chromosome 11. Deletion characterization was performed with FISH cohybridizations; a minimum of 25 bone marrow metaphases was analyzed for each experiment. The BAC/PAC probes belong to RPCI-5 (prefix dJ), RPCI-11/1 (prefix bA), or Caltech (prefix bK) libraries. The mapping of clones and genes was performed by querying the University of California Santa Cruz (UCSC) database (November 2002 release. Available at: http://genome.ucsc.edu/). Each clone was first tested on normal human metaphases. 2.4. Case report In February 2002, a 63-year-old female was admitted to our institution with leukocytosis and anemia. Analysis of peripheral blood confirmed leukocytosis (white blood cell count 69.7 × 109/L) with 73% neutrophils, 5% lymphocytes, 2% monocytes, 2% basophils, 2% eosinophils, 9% metamyelocytes, and 7% myelocytes. Bone marrow cytology showed 2% blasts and 3% promyelocytes. Cytogenetic analysis revealed 46,XX,t(9;22;11)(q34;q11;q13)[25]. Reverse-transcriptase polymerase chain reaction demonstrated the P210 rearrangement (b2a2). The diagnosis of chronic-phase CML was made. The Sokal and Euro risks were intermediate. The patient started treatment with hydroxyurea but obtained no response to therapy. In October 2002, she started imatinib therapy and is now is doing well in hematologic remission.
3. Results The FISH studies with WCPs specific for chromosomes 9, 11, and 22 confirmed their involvement in the variant complex translocation. In fact, the segment downstream to the BCR gene and the distal portion of chromosome arm 11q were transposed on der(11) and on der(9), respectively (Fig. 1A). Cohybridization with ABL1 and BCR clones revealed a fusion signal on the Ph chromosome. No signal was observed on the der(9) chromosome (Fig. 1B). The use of BAC/PAC clones proximal to ABL1 showed deletions of 2.4 Mb of chromosome 9 sequences on der(9). The breakpoint was mapped between the clones RP11-395P17 and RP11-98H23 (540 kb apart). Moreover, a 1.3-Mb deletion of chromosome 22 sequences was revealed through BAC/PAC clones distal to the BCR gene; the breakpoint was located between the clones bA297B9 and bA205J5 (548 kb apart) (Fig. 1C). About 40 genes with known function were lost with deleted sequences on chromosomes 9 and 22. Among these, three are tumor suppressor genes: PTGES (prostaglandin E synthase) on 9q34 and SMARCB1 (SWI/
SNF related, matrix associated, actin dependent regulator of the chromatin subfamily b, member 1) and GSTT1 (glutathione S-transferase theta 1) on 22q11. PTGES, strongly induced by p53, encodes a microsomal glutathione S-transferase and is implicated in apoptosis [7]. The SMARCB1 protein alters chromatin organization at specific DNA sites and may play a role in oncogenesis [8]. The product of the GSTT1 gene is a member of the theta class of glutathione S-transferases, involved in detoxification of carcinogens. Loss of GSTT1 expression has been reported in myelodysplastic syndromes and acute myelocytic leukemia patients [9]. The breakpoint characterization on chromosome 11 with appropriate BAC/PAC clones allowed us to identify a 1.2-Mb deletion in 11q13.1, between bA665N17 [partially deleted on der(11)] and bA755F10 [retained on der(9)](Fig. 1C). Thirty-five genes with known function are located in this deleted region. Three of these genes are involved in the apoptotic mechanism and in cancer cell proliferation: REQ (requiem, apoptosis response zinc finger gene), HTATIP (HIV-1 Tat interactive protein), and CST6 (cystatin E/M). The REQ protein seems to have a regulatory role in rapid hematopoietic cell growth and turnover [10]. The HTATIP protein is a histone acetylase with a role in DNA repair and apoptosis; loss of its activity results in cells with defective double-strand DNA break repair and loss of apoptotic competence [11]. CST6 is a member of the type 2 cystatin gene family, a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions [12]. 4. Discussion We report a CML case with a complex variant translocation, bearing extensive deletions adjacent to the breakpoint of the derivative chromosome 11 in addition to deletions on the der(9). To our knowledge, our case is the fourth CML patient reported to have a complex variant rearrangement characterized by genomic sequences loss on the third derivative chromosome, other than deletions on der(9) [4]. Querying the UCSC database, we identified 75 genes with known function mapping inside the deleted sequences. We focused our attention on genes involved in the regulation of cell proliferation and in the apoptotic pathway, assuming these genes to have a more direct involvement in the neoplastic process. It must also be considered, in this respect, that the single copy loss of these genes can affect cancer cell development and increase the occurrence of new mutations by a haplo-insufficiency mechanism [13]. In our case, we observed the loss of three tumor suppressor genes on der(9) previously reported in CML patients [4]. Three genes (REQ, HTATIP, and CST6) located on the der(11) deleted segment were of particular interest. The REQ and HTATIP proteins have a role in the apoptotic process, whereas loss of expression of CST6 in breast cancer cells has been pointed out as likely associated with a metastatic phenotype in the progression of the primary tumor [10–12].
L. Anelli et al. / Cancer Genetics and Cytogenetics 148 (2004) 137–140
139
Fig. 1. (A) Cohybridization FISH experiment using WCP-11 (red) and WCP-9 (green), showing the presence of a three-way translocation. (B) FISH analysis using PACs dJ1132H12 and dJ835J22 specific for ABL1 (red) and BAC bA164N13 specific for BCR (green), revealing the loss of the reciprocal fusion gene 5′ABL1/3′BCR on the der(9) chromosome. (C) Diagram of the results obtained using clones belonging to chromosomes 9, 22, and 11 for the molecular– cytogenetic characterization of chromosomal breakpoints. White and gray boxes stand for probes retained on der(9) and on der(11), respectively; deleted clones are represented by black boxes.
Although the few reported cases are undoubtedly insufficient to be able to draw any conclusion on the involvement of specific genes in CML pathogenesis, nevertheless these findings indicate that a detailed cytogenetic characterization of CML variant cases is crucial to identify the loss of genomic sequences and to evaluate the occurrence of deletions on the third chromosome involved in the rearrangement.
Acknowledgments The financial support of Associazione Italiana contro le Leucemie-BARI and Ministero dell’Istruzione dell’Universita` e della Ricerca is gratefully acknowledged.
References [1] Mitelman F, Johansson B, Mertens F, editors. Mitelman database of chromosome aberrations in cancer [Internet]. Updated February 2003. Available at: http://cgap.nci.nih.gov/Chromosomes/Mitelman. [2] Hagemeijer A, de Klein A, Godde-Salz E, Turc-Carel C, Smit EM, van Agthoven AJ, Grosveld GC. Translocation of c-abl1 to “masked” Ph in chronic myeloid leukemia. Cancer Genet Cytogenet 1985;18:95–104. [3] Sinclair PB, Nacheva EP, Leversha M, Telford N, Chang J, Reid A, Bench A, Champion K, Huntly B, Green AR. Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia. Blood 2000; 95:738–43. [4] Albano F, Specchia G, Anelli L, Zagaria A, Storlazzi CT, Buquicchio C, Roberti MG, Liso V, Rocchi M. Genomic deletions on other chromosomes involved in variant t(9;22) chronic myeloid leukemia cases. Genes Chromosomes Cancer 2003;36:353–60.
140
L. Anelli et al. / Cancer Genetics and Cytogenetics 148 (2004) 137–140
[5] Mitelman F, editor. An international system for human cytogenetic nomenclature. Basel: S. Karger, 1995. [6] Storlazzi CT, Specchia G, Anelli L, Albano F, Pastore D, Zagaria A, Rocchi M, Liso V. Breakpoint characterization of der(9) deletions in CML patients. Genes Chromosomes Cancer 2002;35:271–6. [7] Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B. A model for p53-induced apoptosis. Nature 1997;389:300–5. [8] Sevenet N, Lellouch-Tubiana A, Schofield D, Hoang-Xuan K, Gessler M, Birnbaum D, Jeanpierre C, Jouvet A, Delattre O. Spectrum of hSNF5/INI1 somatic mutations in human cancer and genotype-phenotype correlations. Hum Mol Genet 1999;8:2359–68. [9] Chen H, Sandler DP, Taylor JA, Shore DL, Liu E, Bloomfield CD, Bell DA. Increased risk for myelodysplastic syndromes in individuals
[10]
[11]
[12]
[13]
with glutathione transferase theta 1 (GSTT1) gene defect. Lancet 1996;347:295–7. Gabig TG, Mantel PL, Rosli R, Crean CD. Requiem: a novel zinc finger gene essential for apoptosis in myeloid cells. J Biol Chem 1994;269:29515–9. Ikura T, Ogryzko VV, Grigoriev M, Groisman R, Wang J, Horikoshi M, Scully R, Qin J, Nakatani Y. Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis. Cell 2000;102:463–73. Sotiropoulou G, Anisowicz A, Sager R. Identification, cloning, and characterization of cystatin M, a novel cysteine proteinase inhibitor, down-regulated in breast cancer. J Biol Chem 1997;272:903–10. Quon KC, Berns A. Haplo-insufficiency? Let me count the ways. Gene Dev 2001;15:2917–21.
Short communication
A chronic myelocytic leukemia case bearing deletions on the three chromosomes involved in a variant t(9;22;11) Luisa Anellia,b, Francesco Albanoc, Antonella Zagariaa,c, Arcangelo Lisoc, Maria Grazia Robertib, Mariano Rocchia, Giorgina Specchiab,c,* a
Sezione di Genetica, Dipartimento di Anatomia Patologica e Genetica, University of Bari, Bari, Italy b Department of Hematology, University and Hospital of Foggia, Foggia, Italy c Department of Hematology, University of Bari, Policlinico, Piazza G. Cesare 11, 70124 Bari, Italy Received 21 April 2003; received in revised form 27 May 2003; accepted 30 May 2003
Abstract
Genomic deletions on the derivative chromosomes bearing the reciprocal fusion gene have recently been reported in chronic myelocytic leukemia (CML). We here describe a CML case with a variant rearrangement t(9;22;11)(q34;q11;q13) showing the loss of chromosome 11 sequences in addition to der(9) deletions. Known tumor suppressor genes involved in apoptosis and in the control of cell proliferation were found to be mapped to the lost sequences. Our findings indicate that genomic deletions may occur also on the third derivative chromosome in variant t(9;22). 쑖 2004 Elsevier Inc. All rights reserved.
1. Introduction
2. Materials and methods
Approximately 90%–95% of chronic myelocytic leukemia (CML) cases are characterized by the Philadelphia chromosome (Ph), which arises from the reciprocal t(9;22)(q34;q11). About 5%–10% of CML patients show a variant translocation, involving one or more chromosomes in addition to 9 and 22. Three-, four-, and five-way variant translocations have been reported [1]. In the majority of variant translocations, the Ph chromosome is cytogenetically detectable, but in rare cases it is masked in the form of additional material transposed on the derivative chromosome 22 [2]. Genomic deletions on the derivative chromosomes bearing the reciprocal fusion gene have recently been observed in CML [3]. In a previous article, we reported three CML cases with complex variant translocations, showing deletions on the third chromosome, in addition to deletions of chromosomes 9 and 22 sequences [4]. We describe a new CML case with a three-way variant rearrangement, carrying genomic deletions on the third chromosome involved in the translocation in addition to deletions on der(9).
2.1. Cytogenetic analysis Conventional cytogenetic analysis of a 24- to 48-hour culture was performed on bone marrow cells at diagnosis with standard techniques and evaluated with Giemsa–trypsin–Giemsa banding at about the 400-band level according to International System for Human Cytogenetic Nomenclature (ISCN 1995) [5]. Twenty-five metaphases were scored. 2.2. FISH studies Fluorescence in situ hybridization (FISH) experiments were performed at diagnosis on bone marrow samples. Chromosome preparations were hybridized in situ with probes labeled with Cy3 and FluorX (Amersham, Piscataway, NJ) by nick translation. Digital images were obtained using a Leica DMRXA epifluorescence microscope equipped with a cooled charge-coupled device camera. Cy3 (red), FluorX (green), and 4′,6-diamidino-2-phenylindole (DAPI; blue) fluorescence signals, detected using specific filters, were recorded separately as gray-scale images. Pseudocoloring and merging of images were performed using Adobe Photoshop software. 2.3. Whole chromosome paint (WCP) and probes
* Corresponding author. Tel.: +39-80-5478711; fax ⫹39-80-5428978. E-mail address: [email protected] (G. Specchia). 0165-4608/04/$ – see front matter 쑖 2004 Elsevier Inc. All rights reserved. doi:10.1016/S0165-4608(03)00246-2
WCPs for chromosomes 9, 11, and 22, obtained from flow-sorted chromosomes, were supplied by the Wellcome
138
L. Anelli et al. / Cancer Genetics and Cytogenetics 148 (2004) 137–140
Trust Sanger Institute, Hinxton, UK. The ABL1 gene was identified by using a pool of the two overlapping P1-derived artificial chromosomes (PACs) dJ835J22 and dJ1132H12; bacterial artificial chromosome (BAC) bA164N13 encompasses the major breakpoint region of the BCR gene [6]. To identify all the breakpoints, we used 15 probes proximal to ABL1, 11 clones distal to BCR, and 12 probes for chromosome 11. Deletion characterization was performed with FISH cohybridizations; a minimum of 25 bone marrow metaphases was analyzed for each experiment. The BAC/PAC probes belong to RPCI-5 (prefix dJ), RPCI-11/1 (prefix bA), or Caltech (prefix bK) libraries. The mapping of clones and genes was performed by querying the University of California Santa Cruz (UCSC) database (November 2002 release. Available at: http://genome.ucsc.edu/). Each clone was first tested on normal human metaphases. 2.4. Case report In February 2002, a 63-year-old female was admitted to our institution with leukocytosis and anemia. Analysis of peripheral blood confirmed leukocytosis (white blood cell count 69.7 × 109/L) with 73% neutrophils, 5% lymphocytes, 2% monocytes, 2% basophils, 2% eosinophils, 9% metamyelocytes, and 7% myelocytes. Bone marrow cytology showed 2% blasts and 3% promyelocytes. Cytogenetic analysis revealed 46,XX,t(9;22;11)(q34;q11;q13)[25]. Reverse-transcriptase polymerase chain reaction demonstrated the P210 rearrangement (b2a2). The diagnosis of chronic-phase CML was made. The Sokal and Euro risks were intermediate. The patient started treatment with hydroxyurea but obtained no response to therapy. In October 2002, she started imatinib therapy and is now is doing well in hematologic remission.
3. Results The FISH studies with WCPs specific for chromosomes 9, 11, and 22 confirmed their involvement in the variant complex translocation. In fact, the segment downstream to the BCR gene and the distal portion of chromosome arm 11q were transposed on der(11) and on der(9), respectively (Fig. 1A). Cohybridization with ABL1 and BCR clones revealed a fusion signal on the Ph chromosome. No signal was observed on the der(9) chromosome (Fig. 1B). The use of BAC/PAC clones proximal to ABL1 showed deletions of 2.4 Mb of chromosome 9 sequences on der(9). The breakpoint was mapped between the clones RP11-395P17 and RP11-98H23 (540 kb apart). Moreover, a 1.3-Mb deletion of chromosome 22 sequences was revealed through BAC/PAC clones distal to the BCR gene; the breakpoint was located between the clones bA297B9 and bA205J5 (548 kb apart) (Fig. 1C). About 40 genes with known function were lost with deleted sequences on chromosomes 9 and 22. Among these, three are tumor suppressor genes: PTGES (prostaglandin E synthase) on 9q34 and SMARCB1 (SWI/
SNF related, matrix associated, actin dependent regulator of the chromatin subfamily b, member 1) and GSTT1 (glutathione S-transferase theta 1) on 22q11. PTGES, strongly induced by p53, encodes a microsomal glutathione S-transferase and is implicated in apoptosis [7]. The SMARCB1 protein alters chromatin organization at specific DNA sites and may play a role in oncogenesis [8]. The product of the GSTT1 gene is a member of the theta class of glutathione S-transferases, involved in detoxification of carcinogens. Loss of GSTT1 expression has been reported in myelodysplastic syndromes and acute myelocytic leukemia patients [9]. The breakpoint characterization on chromosome 11 with appropriate BAC/PAC clones allowed us to identify a 1.2-Mb deletion in 11q13.1, between bA665N17 [partially deleted on der(11)] and bA755F10 [retained on der(9)](Fig. 1C). Thirty-five genes with known function are located in this deleted region. Three of these genes are involved in the apoptotic mechanism and in cancer cell proliferation: REQ (requiem, apoptosis response zinc finger gene), HTATIP (HIV-1 Tat interactive protein), and CST6 (cystatin E/M). The REQ protein seems to have a regulatory role in rapid hematopoietic cell growth and turnover [10]. The HTATIP protein is a histone acetylase with a role in DNA repair and apoptosis; loss of its activity results in cells with defective double-strand DNA break repair and loss of apoptotic competence [11]. CST6 is a member of the type 2 cystatin gene family, a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions [12]. 4. Discussion We report a CML case with a complex variant translocation, bearing extensive deletions adjacent to the breakpoint of the derivative chromosome 11 in addition to deletions on the der(9). To our knowledge, our case is the fourth CML patient reported to have a complex variant rearrangement characterized by genomic sequences loss on the third derivative chromosome, other than deletions on der(9) [4]. Querying the UCSC database, we identified 75 genes with known function mapping inside the deleted sequences. We focused our attention on genes involved in the regulation of cell proliferation and in the apoptotic pathway, assuming these genes to have a more direct involvement in the neoplastic process. It must also be considered, in this respect, that the single copy loss of these genes can affect cancer cell development and increase the occurrence of new mutations by a haplo-insufficiency mechanism [13]. In our case, we observed the loss of three tumor suppressor genes on der(9) previously reported in CML patients [4]. Three genes (REQ, HTATIP, and CST6) located on the der(11) deleted segment were of particular interest. The REQ and HTATIP proteins have a role in the apoptotic process, whereas loss of expression of CST6 in breast cancer cells has been pointed out as likely associated with a metastatic phenotype in the progression of the primary tumor [10–12].
L. Anelli et al. / Cancer Genetics and Cytogenetics 148 (2004) 137–140
139
Fig. 1. (A) Cohybridization FISH experiment using WCP-11 (red) and WCP-9 (green), showing the presence of a three-way translocation. (B) FISH analysis using PACs dJ1132H12 and dJ835J22 specific for ABL1 (red) and BAC bA164N13 specific for BCR (green), revealing the loss of the reciprocal fusion gene 5′ABL1/3′BCR on the der(9) chromosome. (C) Diagram of the results obtained using clones belonging to chromosomes 9, 22, and 11 for the molecular– cytogenetic characterization of chromosomal breakpoints. White and gray boxes stand for probes retained on der(9) and on der(11), respectively; deleted clones are represented by black boxes.
Although the few reported cases are undoubtedly insufficient to be able to draw any conclusion on the involvement of specific genes in CML pathogenesis, nevertheless these findings indicate that a detailed cytogenetic characterization of CML variant cases is crucial to identify the loss of genomic sequences and to evaluate the occurrence of deletions on the third chromosome involved in the rearrangement.
Acknowledgments The financial support of Associazione Italiana contro le Leucemie-BARI and Ministero dell’Istruzione dell’Universita` e della Ricerca is gratefully acknowledged.
References [1] Mitelman F, Johansson B, Mertens F, editors. Mitelman database of chromosome aberrations in cancer [Internet]. Updated February 2003. Available at: http://cgap.nci.nih.gov/Chromosomes/Mitelman. [2] Hagemeijer A, de Klein A, Godde-Salz E, Turc-Carel C, Smit EM, van Agthoven AJ, Grosveld GC. Translocation of c-abl1 to “masked” Ph in chronic myeloid leukemia. Cancer Genet Cytogenet 1985;18:95–104. [3] Sinclair PB, Nacheva EP, Leversha M, Telford N, Chang J, Reid A, Bench A, Champion K, Huntly B, Green AR. Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia. Blood 2000; 95:738–43. [4] Albano F, Specchia G, Anelli L, Zagaria A, Storlazzi CT, Buquicchio C, Roberti MG, Liso V, Rocchi M. Genomic deletions on other chromosomes involved in variant t(9;22) chronic myeloid leukemia cases. Genes Chromosomes Cancer 2003;36:353–60.
140
L. Anelli et al. / Cancer Genetics and Cytogenetics 148 (2004) 137–140
[5] Mitelman F, editor. An international system for human cytogenetic nomenclature. Basel: S. Karger, 1995. [6] Storlazzi CT, Specchia G, Anelli L, Albano F, Pastore D, Zagaria A, Rocchi M, Liso V. Breakpoint characterization of der(9) deletions in CML patients. Genes Chromosomes Cancer 2002;35:271–6. [7] Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B. A model for p53-induced apoptosis. Nature 1997;389:300–5. [8] Sevenet N, Lellouch-Tubiana A, Schofield D, Hoang-Xuan K, Gessler M, Birnbaum D, Jeanpierre C, Jouvet A, Delattre O. Spectrum of hSNF5/INI1 somatic mutations in human cancer and genotype-phenotype correlations. Hum Mol Genet 1999;8:2359–68. [9] Chen H, Sandler DP, Taylor JA, Shore DL, Liu E, Bloomfield CD, Bell DA. Increased risk for myelodysplastic syndromes in individuals
[10]
[11]
[12]
[13]
with glutathione transferase theta 1 (GSTT1) gene defect. Lancet 1996;347:295–7. Gabig TG, Mantel PL, Rosli R, Crean CD. Requiem: a novel zinc finger gene essential for apoptosis in myeloid cells. J Biol Chem 1994;269:29515–9. Ikura T, Ogryzko VV, Grigoriev M, Groisman R, Wang J, Horikoshi M, Scully R, Qin J, Nakatani Y. Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis. Cell 2000;102:463–73. Sotiropoulou G, Anisowicz A, Sager R. Identification, cloning, and characterization of cystatin M, a novel cysteine proteinase inhibitor, down-regulated in breast cancer. J Biol Chem 1997;272:903–10. Quon KC, Berns A. Haplo-insufficiency? Let me count the ways. Gene Dev 2001;15:2917–21.