ICD-Topo |
C420,C421,C424 |
ICD-Morpho |
9680/3 Diffuse large B-cell lymphoma (DLBCL), NOS; Primary DLBCL of the CNS; Primary cutaneous DLBCL, leg type; EBV positive DLBCL of the elderly; DLBCL associated with chronic inflammation; B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma
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ICD-Morpho |
9827/3 Adult T-cell leukaemia/lymphoma
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ICD-Morpho |
9690/3 Follicular lymphoma; Paediatric follicular lymphoma
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ICD-Morpho |
9732/3 Plasma cell myeloma / Multiple myeloma
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ICD-Morpho |
9702/3 Peripheral T-cell lymphoma, NOS; Anaplastic large cell lymphoma, ALK negative
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ICD-Morpho |
9652/3 Mixed cellularity classical Hodgkin lymphoma
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ICD-Morpho |
9699/3 Extranodal marginal zone lymphoma of mucosa- associated lymphoid tissue (MALT lymphoma); Nodal marginal zone lymphoma; Paediatric nodal marginal zone lymphoma
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ICD-Morpho |
9811/3 B lymphoblastic leukaemia/lymphoma, NOS
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ICD-Morpho |
9673/3 Mantle cell lymphoma
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ICD-Morpho |
9874/3 AML with maturation
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ICD-Morpho |
9896/3 AML with t(8;21)(q22;q22); RUNX1-RUNX1T1
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ICD-Morpho |
9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
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ICD-Morpho |
9950/3 Polycythaemia vera
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Atlas_Id |
1052 |
Note |
Isochromosome 18q is an unbalanced structural abnormality in which the short arm is lost and the remaining long arm is duplicated resulting in a chromosome consisting of two identical long arms. i(18)(q10) is a rare chromosome aberration found in a large spectrum of hematological malignances (61 cases), most frequently in older patients (average age 58.3 years) with complex karyotypes. The anomaly was described predominantly in lymphoproliferative disorders (54 cases), but a small number of cases with myeloid malignances and i(18q) were also reported. Isochromosome 18q resulted in a decrease and increase in gene dosage from the monosomy of the 18p arm and trisomy of the 18q arm, respectively. |
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Figure 1 i(18)(q10;q10) - partial G-banding karyotypes of the homologues 18; Fluorescence in situ hybridization with BCL2 (18q21) break probe (Kreatech Diagnostic; Leica) showing three normal fusion signals for BCL2 - one in the long arm of the normal homolog 18 (red arrow) and one in each arm of the abnormal homolog 18 (green arrow); (patient with polycythemia vera, unpublished case - Lubomir Mitev, Lilya Grachlyova, Aselina Asenova). |
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Disease |
Diffuse large B-cell lymphoma (DLBCL) |
Epidemiology | i(18)(q10) is found in 1.5% of DLBCL cases with an abnormal karyotype. Microarray DNA comparative genome hybridization studies have demonstrated that the incidence of 18q11.2-23 gains are 54% in the activated B-cell-like DLBCL and suggested that i(18q) is possibly much more frequent in this subtype of DLBCL (Nedomova et al.,2013). In BCL2 expressing germinal center B-cell-like DLBCL, the 18q11.2-23 gains were found more frequently in Chinese than in Western cases (Chen et al.,2010). Sex ratio of the cases with i(18q) is significantly unbalanced, near M:F=1.8:1 and the anomaly was observed mostly in older patient (average age 59.6 years; range 17-84). |
Cytogenetics | Isochromosome 18q is presented in two types - single copy of i(18q) (41% of the cases) and supernumerary type i(18q) (59% of the cases) which included two or three copies of i(18q). Supernumerary type is frequently associated with +18 and the final number of the long arms of chromosome 18 in these cases reached 6 or 7 copies. All cases in the group of DLBCL are with complex karyotypes. In 12 cases (55%) i(18q) is associated with del(6q) and in 6 cases (27%) with +3. Rearrangements in band 3q27 were seen in one case and t(8;14)(q24;q32) in three cases, respectively. There is no case with t(14;18)(q32;q21). |
Genes | As a result of duplication (single copy of i(18q)) or amplification (supernumerary i(18)(q10) ) of 18q, the expression of the genes located in the regions of the long arm of chromosome 18 are deregulated. Both genes BCL2 and NFATC1 located in 18q21 and 18q23 respectively contribute to the pathogenesis of DLBCL (Nedomova et al., 2013): BCL2 is an anti-apoptotic gene participating in the differentiation of B cells and inhibiting programmed cell death. The deregulation of BCL2 expression is highly associated with t(14;18)(q32;q21) in follicular lymphoma and germinal center B-cell-like DLBCL. The elevated expression of BCL2 due to a gain of 18q is accepted as an alternative mechanism of gene upregulation observed mainly in the cases with ABC DLBCL. NFATC1 is a member of NATF (nuclear factor of activated T cell) family of transcriptional factors that regulates genes involved in the cell cycle, apoptosis and angiogenesis. NFATC1 is frequently overexpressed in the cases of ABC DLBCL. |
Prognosis | Prognosis of patients with i(18)(q10) is poor and this seems to be related to the additional copies of BCL2 oncogene (located in 18q21) leading to overproduction of BCL2 protein (Lu et al.,2015). |
Disease |
Adult-T cell leukemia (ATL) |
Epidemiology | i(18)(q10) is found in 3.5% of ATL cases with an abnormal karyotype. The sex ratio is M:F=1.3:1. The anomaly was described only in older patients (average age 65.1 years; range 52-85). |
Cytogenetics | In 7 cases i(18q) is found in complex karyotypes. In one case it was a second event appearing after clonal evolution of the disease, and in one it was a sole anomaly. In all cases except one i(18q) is presented with one copy in the karyotype. The case with supernumerary i(18)(q10) is associated with +18 and the final number of the copies of i(18q) in this case is 9. In 5 cases (56%) i(18q) is associated with sex chromosome abnormalities (one with structural aberration, two with -X and two with -Y). |
Genes | A candidate gene possibly linked to the pathogenesis of the cases with ATL and i(18q) is PTPN2 (mapped on 18p11.21). The protein encoded by PTPN2 (Tyrosin-protein phosphatase non-receptor type2) is a member of the protein tyrosine phosphatase family that functions as a negative regulator of multiple signaling pathways including IL2 (interleukin 2) mediated JAK/STAT cascade. PTPN2 is inactivated by nonsense mutation in 5% and deleted in 6% of the cases with adult acute T-cell lymphoblastic leukemia (Kleppe et al.,2010; Kleppe ae al.,2011). At the same time deregulation of JAK/STAT pathway is a frequent event in ATL (Takemoto et al.,1997) and one of the reason for this could be 18p deletion, respectively loss of PTPN2 as a result of i(18q). |
Prognosis | It is not clear if there is a difference of the prognosis between the cases with ATL carrying i(18q) and the cases without the anomaly because of the small number of the reported cases with i(18q). |
der(9;18)(p10;q10) |
Bacher, U ; Haferlach, C |
Atlas Genet Cytogenet Oncol Haematol. 2007;11(1):34-35. http://AtlasGeneticsOncology.org/Anomalies/der918p10q10ID1418.html |
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Mutation analysis of the tyrosine phosphatase PTPN2 in Hodgkin's lymphoma and T-cell non-Hodgkin's lymphoma. |
Kleppe M, Tousseyn T, Geissinger E, Kalender Atak Z, Aerts S, Rosenwald A, Wlodarska I, Cools J |
Haematologica 2011 Nov;96(11):1723-7. doi: 10.3324/haematol.2011.041921. Epub 2011 Jul 26. |
PMID 21791476 |
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Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia. |
Kleppe M, Lahortiga I, El Chaar T, De Keersmaecker K, Mentens N, Graux C, Van Roosbroeck K, Ferrando AA, Langerak AW, Meijerink JP, Sigaux F,Haferlach T, Wlodarska I, Vandenberghe P, Soulier J, Cools J |
Nature Genetics 2010 Jun;42(6):530-5. doi: 10.1038/ng.587. Epub 2010 May 16. |
PMID 20473312 |
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Mitelman Database of Chromosome Aberration in Cancer |
Mitelman F, Johansson B and Mertens F |
https://cgap.nci.nih.gov |
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Cytogenetics and molecular cytogenetics in diffuse large B-cell lymphoma (DLBCL). |
Nedomova R, Papajik T, Prochazka V, Indrak K, Jarosova M. |
http://biomed.papers.upol.cz 2013 Sep;157(3):239-47. doi: 10.5507/bp.2012.085. Epub 2012 Nov 6. |
PMID 23132512 |
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Proliferation of adult T cell leukemia/lymphoma cells is associated with the constitutive activation of JAK/STAT proteins. |
Takemoto S, Mulloy JC, Cereseto A, Migone TS, Patel BK, Matsuoka M, Yamaguchi K, Takatsuki K, Kamihira S, White JD, Leonard WJ, Waldmann T,Franchini G |
Proceedings of the National Academy of Sciences of the United States of America 1997 Dec 9; 94(25): 13897-13902. |
PMID 9391124 |
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MYC or BCL2 copy number aberration is a strong predictor of outcome in patients with diffuse large B-cell lymphoma |
Ting-Xun Lu, Lei Fan, Li Wang, Jia-Zhu Wu, Kou-Rong Miao, Jin-Hua Liang, Qi-Xing Gong, Zhen Wang, Ken H. Young, Wei Xu, Zhi-Hong Zhang, and Jian-Yong Li |
Oncotarget 2015 Jul 30;6(21):18374-88. |
PMID 4621897 |
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Diffuse Large B-Cell Lymphoma in Chinese Patients Immunophenotypic and Cytogenetic Analyses of 124 Cases |
Yan Chen MD, Tao Han MD, Javeed Iqbal PhD, Richard Irons PhD, Wing C. Chan MD, Xiongzeng Zhu MD, Kai Fu MD, PhD |
American journal of clinical pathology 2010 Feb;133(2):305-13 |
PMID 20093241 |
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