STRUCTURAL ABERRATIONS OF 1p36 IN HEMATOLOGIC MALIGNANCIES

Abstract

Objective: Structural aberrations of 1p36 are very common in most hematologic malignancies. 1p36 consists of genes that are important in oncogenesis. The aim of this study was to define 1p36 abnormalities and their distributions within different hematologic malignancies. Materials and Methods: To achieve this goal, we retrospectively evaluated the cytogenetic results of our hematological cancer cases. Result: We found deletions or rearrangements of breakpoint 1p36 in 18 patients with various hematologic malignancies, including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), multiple myeloma (MM), chronic myeloid leukemia (CML), lymphoma, B cell acute lymphoblastic leukemia (B-ALL), idiopathic thrombocytopenic purpura (ITP) and aplastic anemia (AA). We observed t(1;3)(p36;p21) in one AML-M2 patient and t(1;3)(p36;q21) in two CML patients. Eight patients (1 MDS, 2 MM, 3 CML, 1 AML, and 1 AA) had translocations and rearrangements. One ITP patient had der(1)t(1;1)(p36;q21) and another CML patient had der(1)t(1;1)(p36;q12). We demonstrated several terminal deletions with different breakpoints between 1p11 and 1p36 in five patients, (2 MDS, 2 lymphomas, and 1 B cell acute lymphocytic leukemia). Conclusion: The 1p36 breakpoint is a hot spot for cancer-related chromosome rearrangements and is associated with poor prognosis. In order to emphasize the importance of 1p36 in hematologic malignancies it essential to build a large data pool on the subject. The distribution of breakpoints in 1p abnormalities in our series was remarkable, as 12 out of 18 1p breakpoints were 1p36. However, while 1p breakpoints aggregated on 1p36 in all translocations, there was only one 1p36 breakpoint in five deletions. With this paper, we contribute to the relevant literature by reporting our results.

Keywords

• 1p36
• leukemia
• lymphoid malignancies
• myeloid malignancies
• cytogenetics
• bone marrow

Supporting Institution

İstanbul Üniversitesi Araştırma Fonu

Project Number

25328

Thanks

Thanks to Mine Gürsel for the English grammar corrections.

HEMATOLOJİK KANSERLERDE 1p36’NIN YAPISAL ANOMALİLERİ

Abstract

Amaç: 1p36 bölgesinin yapı anomalileri bir çok hematolojik kanserde oldukça yaygındır. 1p36 bölgesi, kanser gelişiminde etkili olan önemli genlere sahiptir. Bu çalışmanın amacı, olgularımıza ait 1p36 anomalilerini ve farklı hematolojik kanserlerdeki dağılımlarını belirtmektir. Gereç ve Yöntem: Bu çalışma için hematolojik kanser olgularımızın sitogenetik sonuçları retrospektif olarak değerlendirilmiştir. Bulgular: Myelodisplastik sendrom (MDS), akut myeloid lösemi (AML), multipl myelom (MM), kronik myeloid lösemi (KML), lenfoma, B hücreli akut lenfoblastik lösemi (B-ALL), idyopatik trombositopenik purpura (ITP) ve aplastik anemi (AA) hastası olmak üzere 18 farklı hematolojik kanser olgusunda 1p36 kırık noktasına ait delesyon ya da yeniden düzenlenmeler saptanmıştır. Bir AML-M2 hastasında t(1;3)(p36;p21) ve iki KML hastasında t(1;3) (p36;q21) gözlemlenirken, sekiz hastada (1 MDS, 2 MM, 3 KML, 1 AML and 1 AA) translokasyon ve yeniden düzenlenmeler tespit edilmiştir. Bir ITP hastası der(1)t(1;1)(p36;q21) ve bir KML hastasında ise der(1)t(1;1)(p36;q12) kromozom yapısı saptanmıştır. Beş hastada (2 MDS, 2 lenfoma, ve 1 B hücreli akut lenfositik lösemi) 1p11 ve 1p36 arasındaki farklı kırık noktalarında çeşitli terminal delesyonlar gözlenmiştir. Sonuç: 1p36 kanserle ilişkili kromozom yeniden düzenlemeler için sıcak noktadır ve kötü prognozla ilişkilendirilmektedir. 1p36 bölgesinin hematolojik kanserlerdeki önemini vurgulamak için, konuyla ilgili geniş bir veri havuzu oluşturmak önemlidir. Serimizdeki 1p36 anomalilerinin dağılımı, 18 hastanın 12’sinde 1p kırık noktasının 1p36 olması nedeniyle dikkat çekicidir. Bu çalışma ile sonuçlarımızı sunarak bu alandaki literatüre katkı sağlayacağımızı düşünmekteyiz.

Keywords

• 1p36
• lösemi
• lenfoid kanserler
• myeloid kanserler
• sitogenetik
• kemik iliği

Project Number

25328

References

1. Sato Y, Izumi T, Kanamori H, Davis EM, Miura Y, Larson RA et al. t(1;3)(p36;p21) Is a Recurring Therapy-Related Translocation. Genes Chromosomes Cancer 2002;34(2):186-92. [CrossRef] google scholar
2. Yoshida C, Suzukawa K, Katsura Y, Shimizu S, Mukai HY, Hasegawa Y et al. T-cell acute lymphoblastic leukemia with add(1)(p36) and del(12)(p11) following acute myelocytic leukemia with partial deletion of 9p. Cancer Genet Cytogenet 2004;150(1):62-5. [CrossRef] google scholar
3. Xian RR, Xie Y, Haley LM, Yonescu R, Pallavajjala A, Pittaluga S et al. CREBBP and STAT6 co-mutation and 16p13 and 1p36 loss define the t(14;18)-negative diffuse variant of follicular lymphoma. Blood Cancer J 2020;10(69):1-12. [CrossRef] google scholar
4. Lahortiga I, Vazquez I, Belloni E, Roman JP, Gasparini P, Novo FJ et al. FISH analysis of hematological neoplasias with 1p36 rearrangements allows the definition of a cluster of 2.5 Mb included in the minimal region deleted in 1p36 deletion syndrome. Hum Genet 2005;116(6):476-85. [CrossRef] google scholar
5. Caramazza D, Hussein K, Siragusa S, Pardanani A, Knudson RA, Ketterling RP et al. Chromosome 1 abnormalities in myeloid malignancies: a literatüre survey and karyotype-phenotype associations. Eur.J.Haematol 2009;84(3):191-200. [CrossRef] google scholar
6. Chng,WJ, Gertz MA, Chung T-H, Wier SV, Keats JJ, Baker A et al. Correlation between array-comparative genomic hybridization defined genomic gains and losses and survival: identification of 1p31-32 deletion as a prognostic factor in myeloma. Leukemia 2010;24(4):833-42. [CrossRef] google scholar
7. Barasch NK, Liu YC, Ho J, Bailey N, Aggarwal N, Cook JR et al. The molecular landscape and other distinctive features of primary cutaneous follicle center lymphoma. Hum Pathol 2020;106:93-105. [CrossRef] google scholar
8. Nadarajan VS, Phan C-L, Ang C-H, Liang K-L, Gan G-G, Bee P-C et al. Identification of copy number alterations by array comparative genomic hybridization in patients with late chronic or accelerated phase chronic myeloid leukemia treated with imatinib mesylate. Int J Hematol 2011;93(4):65-73. [CrossRef] google scholar

9. Duhoux FP, Ameye G, Montano-Almendras CP, Bahloula K, Mozziconacci MJ, Laibe S et al. PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies. Br J of Haematol 2012;156(1):76-88. [CrossRef] google scholar
10. Gudmundssona KO, Nguyena N, Oakleya K, Han Y, Gudmundsdottir B et al. Prdm16 is a critical regulator of adult long-term hematopoietic stem cell quiescence. PNAS 2020;117(50):31945-53. [CrossRef] google scholar
11. Dao F-T, Chen W-M, Long L-Y, Lİ L-D, Yang L, Wang J et al. High PRDM16 expression predicts poor outcomes in adult acute myeloid leukemia patients with intermediate cytogenetic risk: a comprehensive cohort study from a single Chinese center. Leuk Lymphoma 2021;62(1):185-93. [CrossRef] google scholar
12. McDonald JM, Dunmire V, Taylor E, Sawaya R, Bruner J, Fuller GN et al. Attenuated Expression of DFFB is a Hallmark of Oligodendrogliomas with 1p-Allelic Loss. Mol Cancer 2005;4:35 [CrossRef] google scholar
13. Seto KKY and Andrulis IL. Atypical Protein Kinase C Zeta: Potential Player in Cell Survival and Cell Migration of Ovarian Cancer. Plos One 2015;10(4):e0123528 [CrossRef] google scholar
14. MMP23B Gene - Matrix Metallopeptidase 23B. Protein Coding (Updated: Aug 2, 2023 ; GC01P006089 ; GIFtS: 42 ). Available from: URL: https://www.genecards.org/cgi-bin/ carddisp.pl?gene=MMP23B google scholar
15. Masetti R,Togni M, Astolfi A, Pigazzi M, Indio V, Rivalta B et al. Whole transcriptome sequencing of a paediatric case of de novo acute myeloid leukaemia with del(5q) reveals RUNX1-USP42 and PRDM16-SKI fusion transcripts. Br J of Haematol 2014;166(3):449-52. [CrossRef] google scholar
16. Tesser-Gamba F, Petrilli AS, Alves MS, Juliano RJGFY, Toledo SRC. MAPK7 and MAP2K4 as prognostic markers in osteosarcoma. Hum Pathol 2012;43(7):994-1002 [CrossRef] google scholar
17. Rooney DE, Czepulkowski BH, editors. Human Cytogenetics-A Practical Approach. Oxford: IRL Press; Vol II, 1987. google scholar
18. McGowan-Jordan J, Simon A, Schmid M, editors. ISCN 2016, An International System for Human Cytogenetic Nomenclature. Basel: Karger AG; 2016. [CrossRef] google scholar
19. Güven GS, Tarkan Argüden Y, Öngören Ş, Deviren A, Aydın Y, Hacıhanefioğlu S. t(1;3)(p36;p21): presentation of a patient with MDS/AML (M2) and review of the literature. Turk J Hematol 2006;23(2):115-8. google scholar
20. Johansson B, Fioretos T, Mitelman F. Cytogenetic and Molecular Genetic Evolution of Chronic Myeloid Leukemia. Acta Haematol 2002;107(2):76-94. [CrossRef] google scholar
21. Brazma D, Grace C, Howard J, Melo JV, Holyoke T, Apperley JF et al. Genomic Profile of Chronic Myelogenous Leukemia: Imbalances Associated with Disease Progression. Genes Chromosomes Cancer 2007;46(11):1039-50. [CrossRef] google scholar
22. Duhoux FP, Ameye G, Lambot V, Herens C, Lambert F, Raynaud S et al. Refinement of 1p36 Alterations Not Involving PRDM16 in Myeloid and Lymphoid Malignancies. PLoS One 2011;6(10):e26311. [CrossRef] google scholar
23. Atlas. Hosted by INIST Last update: Wed May 26 17:52:44 CEST 2021 http://atlasgeneticsoncology.org google scholar
24. Lunghi M, Casorzo L, De Paoli L, Riccomagno P, Rossi D, Gaidano G. Derivative (1)t(1;16)(p11;p11.1) in myelodysplastic syndrome: a case report and review of the literature. Cancer Genet Cytogenet 2010;196(1):89-92. [CrossRef] google scholar
25. Tantavahi R, Shipp MA, Greeley TA, Pavelkaa K, Bern MM, Rosenthal DS et al. Four patients with myelodysplastic syndrome with translocations (1;7)(p11;p11) including one patient with independent clones del(1)(q22) and t(1;7) (q21;q11). Cancer Genet Cytogenet 1988;30(1):83-90. [CrossRef] google scholar
26. Mohamed AN, Palutke M, Eisenberg L, Al-Katib A. Chromosomal analyses of 52 cases of follicular lymphoma with t(14;18), including blastic/blastoid variant. Cancer Genet Cytogenet 2001;126:45-51. [CrossRef] google scholar
27. Mitsui T, Yokohama A, Koiso H, Saito A, Toyama K, Shimizu H et al. Prognostic impact of trisomy 21 in follicular lymphoma. Br J of Haematol 2018;184(4):570-7. [CrossRef] google scholar
28. Carbone P, Barbata G, Tumminello P, Bellanca F, Majolino I, Granata G. Translocation t(8;14)(q24;q32) and del(1) (p22) in FAB-L1 adult acute lymphoblastic leukemia with long survival. Cancer Genet Cytogenet 1988;32(1):143-7. [CrossRef] google scholar
29. Belaud-Rotureau MA, Marietta V, Vergier B, Mainhaguiet G, Turmo M, Idrissi Y et al. Inactivation of p16INK4a/CDKN2A gene may be a diagnostic feature of large B cell lymphoma leg type among cutaneous B cell lymphomas. Virchows Arch 2008;452(6):607-20. [CrossRef] google scholar
30. Coupland, LA, Jammu, V, Pidcock, ME. Partial deletion of chromosome 1 in a case of acute myelocytic leukemia. Cancer Genet Cytogenet 2002;139(1):60-2.. [CrossRef] google scholar
31. Svobodova K, Zemanova Z, Lhotska H, Novakovaa M, Podskalska L, Belickova M et al. Copy number neutral loss of heterozygosity at 17p and homozygous mutations of TP53 are associated with complex chromosomal aberrations in patients newly diagnosed with myelodysplastic syndromes. Leuk Res 2016 42:7-12. [CrossRef] google scholar
32. Lancman G, Tremblay D, Barley K, Barlogie B, Cho HJ, Jagannath S et al. The Effect of Novel Therapies in High-Molecular-Risk Multiple Myeloma. Clin Adv Hematol Oncol 2017;15(11):870-9. google scholar
33. Wang H, Wang X-Q, Xu X-P, Lin G-W. Cytogenetic evolution correlates with poor prognosis in myelodysplastic syndrome. Cancer Genet Cytogenet 2010;196(2):159-66. [CrossRef] google scholar
34. Kim B-R, Kim J-E, Woo K-S, Kim K-H, Kim J-M, Lee S et al. A Case of Near-triploidy in Myelodysplastic Syndrome with del(5q) Combined with del(1p) and del(13q). Ann Lab Med 2012;32(4):294-7. [CrossRef] google scholar
35. Zamecnikova A and Bahar S. der(1)t(1;1)(p36;q11-q32) in hematopoietic malignancies. Atlas Genet Cytogenet Oncol Haematol 2017;21(4):150-5. [CrossRef] google scholar
36. Pawlyn C, Loehr A, Ashby C, Tytarenko R, Deshpande S, Sun J et al. Multiple myeloma, gammopathies Loss of heterozygosity as a marker of homologous repair deficiency in multiple myeloma: a role for PARP inhibition? Leukemia 2018;32(7):1561-6. [CrossRef] google scholar
37. Aamot HV, Torlakovic EE, Eide MB, Holte H, Heim S. Non-Hodgkin lymphoma with t(14;18): clonal evolution patterns and cytogenetic-pathologic-clinical correlations. J Cancer Res Clin Oncol 2007;133(7):455-70. [CrossRef] google scholar
38. Tsukamoto T, Kiyota M, Kawata E, Uoshima N, Tatekawa S, Chinen Y et al. Detection of chromosomal abnormalities by G-banding and prognostic impact in follicular lymphoma in the rituximab era. Int J Hematol 2017;105(5):658-67 [CrossRef] google scholar
39. Cheung M, Pei J, Pei Y, Pass H I, Testa J R. The promyelocytic leukemia zinc finger gene, PLZF, is frequently downregulated in malignant mesothelioma cells and contributes to cell survival. Oncogene 2010;29(11):1633-40. [CrossRef] google scholar
40. Kreisela F, Kulkarnia S, Kerns RT, Hassan A, Deshmukh H, Nagarajan R et al. High-resolution array comparative genomic hybridization (aCGH) identifies copy number alterations in diffuse large B-cell lymphoma that predict response to immuno-chemotherapy. Cancer Genet 2001;204(3):129-37. [CrossRef] google scholar
41. Poluben L, Bryke CR, Hsu Y, Shumeiko O, Neumerzhitska L, Klimuk B et al. Copy NumberAlterations And Copy-Neutral Loss of Heterozygosity In Ukraınian Patıents With Primary Myelofibrosis. Exp Oncol 2019;41(1):53-6. [CrossRef] google scholar
42. Bozkurt S , Okay M, Sağlam F, Haznedaroğlu İ C. Retrospective evaluation of chromosome 1 anomalies in hematologic malignancies: A single center study. Genetics&Applications 2019;3(3)|:17-24. [CrossRef] google scholar
43. Moir DJ, Jones PA, Pearson J, Duncan JR, Cook P. A new translocation, t(1;3) (p36;q21), in myelodysplastic disorders. Blood 1984;64(2):553-5. [CrossRef] google scholar
44. Bai B, Lu G, Hu S, Yin C. t(1;3)(p36;p21) as the Sole Clonal Abnormality in Refractory Acute Myeloid Leukemia. NA J Med Sci 2012;5(4):235-8. [CrossRef] google scholar
45. Cheung K-JJ, Johnson NA, Affleck JG, Severson T, Steidl C, Ben-Neriah S et al. Acquired TNFRSF14 mutations in follicular lymphoma are associated with worse prognosis. Cancer Res 2010;70(22):9166-74. [CrossRef] google scholar
46. Mori N, Ohwashi-Miyazaki M, Yoshinaga K, Okada M, Shiseki M, Motoji T et al. Tumor suppressor gene methylation on the short arm of chromosome 1 in chronic myelogenous leukemia. Eur J Haematol 2017; 98(5): 467-477. [CrossRef] google scholar
47. Gângo A, Bâtai B, Varga M, Kapczâr D, Papp G, Marschalko M et al. Concomitant 1p36 deletion and TNFRSF14 mutations in primary cutaneous follicle center lymphoma frequently expressing high levels of EZH2 protein. Virchows Archiv 2018;473(4):453-62. [CrossRef] google scholar
48. Martin-Moro F, Marquet-Palomanes J, Piris-Villaespesa M, Lopez-Jimenez J, Garcıa-Cosıo M. Diffuse follicular lymphoma variant with a typical diagnostic pattern and an unusually aggressive clinical presentation. Int J Hematol 2020;112(2):136-8. [CrossRef] google scholar
49. Naderi A. Genomic and epigenetic aberrations of chromosome 1p36.13 have prognostic implications in malignancies. Chromosome Res 2020;28(3-4):307-30 [CrossRef] google scholar
50. Sano K, Hayakawa A, Piao J-H, Kosaka Y, Nakamura H. Novel SH3 protein encoded by the AF3p21 gene is fused to the mixed lineage leukemia protein in a therapy-related leukemia with t(3;11) (p21;q23). Blood 2000;95(3):1066-8. [CrossRef] google scholar