del(18)(p11)

Abstract

Review on del(18)(p11) in haematological malignancies, with data on the genes possibly involved.

Keywords

Chromosome 18; Chronic myeloid leukemia; Myelodysplastic syndromes; Acute myeloid leukemia; Acute lymphoblastic leukemia; Follicular lymphoma

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Identity

ICD-Topo	C420,C421,C424
ICD-Morpho	9873/3 AML without maturation
ICD-Morpho	9874/3 AML with maturation
ICD-Morpho	9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho	9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
ICD-Morpho	9989/3 Myelodysplastic syndrome, unclassifiable
ICD-Morpho	9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho	9837/3 T lymphoblastic leukaemia/lymphoma
ICD-Morpho	9690/3 Follicular lymphoma; Paediatric follicular lymphoma
Atlas_Id	1314

Clinics and Pathology

Note

del(18)(p11) is a very rare structural anomaly found only in 24 cases with onco-hematological disorders. This deletion has been observed in both myeloid (14 cases) and lymphoid (10 cases) malignancies and has been predominantly associated with a complex karyotype. In all cases 18p- is presented as a single copy in the karyotype. The anomaly was determined by conventional cytogenetic as terminal deletion with sub-band location of the breakpoint in 18p11.2. Microarray comparative genome hybridization (aCGH) studies in patients with acute myeloid leukemia have demonstrated that the deleted segment in 18p could be also interstitial and variable in size as has been proven in other tumor associated deletions. Three submicroscopic deleted regions have been identified - 18p11.32-p11.31, 18p11.23 and 18p11.22-p11.21 (Itzhar et al, 2011).

Disease	Acute Myeloid Leukemia (AML)
Epidemiology	del(18)(p11) is found in 9 cases ( 0.1% of all AML cases with an abnormal karyotype) (Alimena et al., 1981; Brodeur et al., 1983; GFCH, 1990; Lawler et al., 1990; Mohamed et al., 1993; Davey et al., 1995; Krauter et al., 1998; Babicka et al., 2007; Kasyan et al., 2010) - 1 case with M1 French-American-British (FAB) phenotype, 2 cases with M2, 1 case with M3, 1 case with M4, 1 case with M6 and 3 with AML, NOS (one diagnosed as therapy related AML). The sex ratio is significantly unbalanced, near M:F=3.5:1. The age is documented in 5 cases: 6 and 35 (M2), 59 (M3), 42 (M4) and 61 (M6).
Cytogenetics	In 5 cases del(18)(p11) is found in complex karyotypes and in one as a sole anomaly. Three cases are with -5/del(5q), two with +8 and one case of each of the following well known rearrangements: -7; del(17p); t(8;21)(q22;q22); t(17;20)(q21;q11) in a M3 ( RARA not checked). In one case both arms of chromosome 18 are affected- der(18)del(18)(p11)del(18)(q21). In 3 cases 18p- is associated with sex chromosome abnormalities - 2 with a loss of Y chromosome and one with del(X)(q26).

Disease	Other Myeloproliferative Disorders
Epidemiology	del(18)(p11) is described in 2 cases (one male and one female) with chronic myeloid leukemia (CML) (Ohyashiki et al., 1997; Sun et al,. 2011), 2 cases (males) with a myelodysplastic syndrome (Cerretini et al., 2002; Volkert et al., 2014) and one case (female) with primary myelofibrosis (PMF) involving a lymph node (Hu et al., 2009).
Cytogenetics	In 2 cases with MDS and one case with CML del(18)(p11) is associated with a complex karyotype, in one case with CML it is a second event and in one case (with PMF) it is a sole anomaly. In the two cases with CML 18p- anomaly is present in additional deviating sub-clones (sidelines) and in one case with MDS in two clones with dic(17;20)(p11-12;q11) and dic(18;18)(p11;p11).

Disease	Acute Lymphoblastic Leukemia (ALL)
Epidemiology	del(18)(p11) is found in 8 cases with ALL (0.08% of all ALL cases with an abnormal karyotype) (Oshimura et al., 1977; Kanerva et al., 2002; van der Burg et al., 2002; Soulier et al., 2003; Karst et al., 2006; Shin et al., 2011; Schmiegelow et al., 2012; Lundin et al., 2014). The sex ratio is significantly unbalanced, near M:F=1.7:1. The anomaly has been observed in young, as well as older patients (average age 22.6 years; range 5-65).
Cytogenetics	In 5 cases del(18)(p11) is found in complex karyotypes and in 3 cases it is accompanied with second anomalies - der(21) in two cases and dup(18q)(q11q11) in one (unrelated clone). In 4 of the 5 cases with complex karyotypes 18p- is associated with one or more deletions including 6p-, 9p-, 11q- and 12p- and in two cases with t(7;14)(p13;q32) and t(14;18)(q32;q21) (Shin et al., 2011), respectively.

Disease	Follicular lymphoma (FL)
Cytogenetics	del(18)(p11) is reported in 2 cases with FL (Bosga-Bouwer et al., 2003; Horsman et al., 2003). Both have hyperdiplpoid, highly complex karyotypes.

Genetics

A tumor suppressor gene(s) (TSG) important to the described hematological malignances may be is involved in the molecular pathogenesis of del(18)(p11). A number of TSG candidates are mapped in the deleted segment 18p11.2->18pter including PTPN2 (18p11.21), LDLRAD4 (C18orf1) (18p11.21), RALBP1 (18p11.22), PPP4R1 (18p11.22), PTPRM (18p11.23), EPB41L3 (18p11.31), L3MBTL4 (18p11.31), TGIF1 (18p11.31), ZEP161 (18p11.31) and SMCHD1 (18p11.32). Almost all are implicated in the pathogenesis of a variety of solid tumors, but there are several lines of data suggesting that four of them (PTPN2, PTPRM, TGIF1 and SMCHD1) could also have a role in leukogenesis and respectively may act as TSG in the hematopoietic system.

Genes involved and Proteins

Gene Name	PTPN2 (protein tyrosine phosphatase, non-receptor type 2)
Location	18p11.21
Protein	PTPN2 (Tyrosine-protein phosphatase non-receptor type2) is a negative regulator of multiple signaling pathways, including IL2 (interleukin 2) mediated JAK2/STAT cascade and 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).

Gene Name	PTPRM (protein tyrosine phosphatase, receptor type M)
Location	18p11.23
Protein	PTPRM (Tyrosine-protein phosphatase, receptor type M) is targeted by aCGH within the deleted region 18p11.23 found in 17 cases with AML. The protein encoded by this gene is involved in cell-cell adhesion through hemophilic interactions. Hypermethylation of PTPRM in cases with ALL (Stevenson et al, 2013) and submicroscopic deletion of PTPRM in cases of adult T cell leukemia/lymphoma have been observed (Kataoka et al 2015).

Gene Name	TGIF1 (TGFB induced factor homeobox 1)
Location	18p11.31
Protein	TGiF1 (TG-interacting factor 1) is targeted by aCGH within the deleted region 18p11.32p11.31 found in 14 cases with AML. The protein encoded by this gene plays an essential role in the regulation of hematopoiesis inhibiting the signaling pathways of RA (retinoic acid) and TGFB1 (transforming growth factor beta) by transcriptional repression of SMAD2. It has been demonstrated that TGIF1 is a negative regulator of KMT2A (MLL)-rearranged AML (Willer et al, 2014).

Gene Name	SMCHD1 (structural maintenance of chromosomes flexible hinge domain containing 1)
Location	18p11.32
Protein	SMCHD1 (Structural maintenance of chromosome flexible hinge domain containing 1) is also targeted by aCGH within the region 18p11.32p11.31.This gene encodes a protein required for the maintenance of an X chromosome inactivation in females. It has been reported that SMCHD1 is associated with increased tumorigenesis in a mouse model. Global gene expressing profiling revealed that SMCHD1 normally repress genes activated by MLL- chimeric fusion proteins in leukemia (Leong et al, 2012). These data have suggested that the loss of SMCHD1 may cause hematological malignances of both cell lineage - myeloid and lymphoid.

Bibliography

Chromosomal Minimal Critical Regions in Therapy-Related Leukemia Appear Different from Those of De Novo Leukemia by High - Resolution aCGH.

Itzhar N, Dessen P, Toujani S,  Auger N,  Preudhomme C, Richon C, Lazar V, Saada V, Bennaceur A, Bourhis J H, de Botton S , and  Bernheim A.

PLoS One. 2011; 6(2): e16623 Published online 2011 Feb 14. doi: 10.1371/journal.pone.0016623

PMID 3038855

Extrachromosomal Gene Amplification in Acute Myeloid Leukemia; Characterization by Metaphase Analysis, Comparative Genomic Hybridization, and Semi-Quantitative PCR.

Mohamed N A, Macoska A J, Kallioniemi A, Kallioniemi P O, Waldman F , Ratanatharathorn V , Wolman R S.

Genes Chromosomes Cancer 8 (3), 185-189. 11 1993.

PMID 750962

Association of the type of 5q loss with complex karyotype, clonal evolution, TP53 mutation status, and prognosis in acute myeloid leukemia and myelodysplastic syndrome.

Volkert S, Kohlmann A, Schnittger S, Kern W, Haferlach T, Haferlach C.

Genes Chromosomes Cancer. 2014 May;53(5):402-10. doi: 10.1002/gcc.22151. Epub 2014 Feb 3.

PMID 24493299

Morphologic Characteristics of Erythroleukemia (Acute Myeloid Leukemia; FAB-M6): A CALGB Study

Davey R F, Abraham N , Brunetto L V , MacCallum M J, Nelson A D ,Ball D E , Griffin D J , Baer R M, Wurster-Hill D , Mayer J R.

Am J Hematol 49 (1), 29-38. 5 1995.

PMID 7741135

Myelofibrosis involving lymph node: a novel cytogenetic abnormality in a mimicker of mesenchymal neoplasm

Hu Y,  Zaslav A, Radhakrishnan N , Golightly M, and  Pameijer C.

J Hematop. 2009 Sep; 2(3): 157-161.

PMID 2766443

Epigenetic regulator Smchd1 functions as a tumor suppressor.

Leong HS, Chen K, Hu Y, Lee S, Corbin J, Pakusch M, Murphy JM, Majewski IJ, Smyth GK, Alexander WS, Hilton DJ, Blewitt ME.

Cancer Res. 2013 Mar 1;73(5):1591-9. doi: 10.1158/0008-5472.CAN-12-3019. Epub 2012 Dec 26.

PMID 23269277

TGIF1 is a negative regulator of MLL-rearranged acute myeloid leukemia.

Willer A, Jakobsen JS, Ohlsson E, Rapin N, Waage J, Billing M, Bullinger L, Karlsson S, Porse BT

Leukemia. 2015 May;29(5):1018-31. doi: 10.1038/leu.2014.307. Epub 2014 Oct 28.

PMID 25349154

Acute lymphocytic and myelomonocytic leukemia associated with low platelet counts and a 21q- marker chromosome.

Alimena G, Dallapiccola B, De Cuia MR, Mandelli F, Mitelman F.

Hum Genet. 1981;57(3):329-31.

PMID 6941924

Analysis of complex chromosomal rearrangements in adult patients with MDS and AML by multicolor FISH.

Babicka L, Ransdorfova S, Brezinova J, Zemanova Z, Sindelarova L, Siskova M, Maaloufova J, Cermak J, Michalova K.

Leuk Res. 2007 Jan;31(1):39-47. Epub 2006 May 9.

PMID Leuk

Follicular lymphoma grade 3B includes 3 cytogenetically defined subgroups with primary t(14;18), 3q27, or other translocations: t(14;18) and 3q27 are mutually exclusive.

Bosga-Bouwer AG, van Imhoff GW, Boonstra R, van der Veen A, Haralambieva E, van den Berg A, de Jong B, Krause V, Palmer MC, Coupland R, Kluin PM, van den Berg E, Poppema S

Blood. 2003 Feb 1;101(3):1149-54.

PMID 12529293

Cytogenetic features of acute nonlymphoblastic leukemia in 73 children and adolescents.

Brodeur GM, Williams DL, Kalwinsky DK, Williams KJ, Dahl GV.

Cancer Genet Cytogenet. 1983 Feb;8(2):93-105.

PMID 6825064

Evaluation of constitutional chromosome aberrations in hematologic disorders.

Cerretini R, Acevedo S, Chena C, Belli C, Larripa I, Slavutsky I.

Cancer Genet Cytogenet. 2002 Apr 15;134(2):133-7

PMID 12034526

Acute myelogenous leukemia with an 8;21 translocation. A report on 148 cases from the Groupe Français de Cytogénétique Hématologique.

GFCH (Groupe Francais de Cytogenetique Hematologique)

Cancer Genet Cytogenet. 1990 Feb;44(2):169-79.

PMID 2297675

Follicular lymphoma lacking the t(14;18)(q32;q21): identification of two disease subtypes.

Horsman DE, Okamoto I, Ludkovski O, Le N, Harder L, Gesk S, Siebert R, Chhanabhai M, Sehn L, Connors JM, Gascoyne RD.

Br J Haematol. 2003 Feb;120(3):424-33.

PMID 12580956

Minimal residual disease by metaphase FISH in children with ALL: clonal cells during or after chemotherapy may not predict relapse.

Kanerva J, Vettenranta K, Autio K, Knuutila S, Saarinen-Pihkala UM.

Leuk Res. 2002 Jun;26(6):545-50

PMID 12007502

Novel cryptic chromosomal rearrangements detected in acute lymphoblastic leukemia detected by application of new multicolor fluorescent in situ hybridization approaches.

Karst C, Gross M, Haase D, Wedding U, Höffken K, Liehr T, Mkrtchyan H

Int J Oncol. 2006 Apr;28(4):891-7.

PMID 16525638

Acute erythroid leukemia as defined in the World Health Organization classification is a rare and pathogenetically heterogeneous disease.

Kasyan A, Medeiros LJ, Zuo Z, Santos FP, Ravandi-Kashani F, Miranda R, Vadhan-Raj S, Koeppen H, Bueso-Ramos CE.

Mod Pathol. 2010 Aug;23(8):1113-26. doi: 10.1038/modpathol.2010.96. Epub 2010 May 14.

PMID  20473273

Integrated molecular analysis of adult T cell leukemia/lymphoma.

Kataoka K, Nagata Y, Kitanaka A, Shiraishi Y, Shimamura T, Yasunaga J, Totoki Y, Chiba K, Sato-Otsubo A, Nagae G, Ishii R Muto S, Kotani S, Watatani Y, Takeda J, Sanada M, Tanaka H, Suzuki H, Sato Y, Shiozawa Y, Yoshizato T, Yoshida K, Makishima H, Iwanaga M, Ma G,Nosaka K, Hishizawa M, Itonaga H, Imaizumi Y, Munakata W, Ogasawara H, Sato T, Sasai K, Muramoto K, Penova M, Kawaguchi T,Nakamura H, Hama N, Shide K, Kubuki Y, Hidaka T, Kameda T, Nakamaki T, Ishiyama K, Miyawaki S, Yoon SS, Tobinai K, Miyazaki Y,Takaori-Kondo A, Matsuda F, Takeuchi K, Nureki O, Aburatani H, Watanabe T, Shibata T, Matsuoka M, Miyano S, Shimoda K, Ogawa S

Nat Genet. 2015 Nov;47(11):1304-15. doi: 10.1038/ng.3415. Epub 2015 Oct 5.

PMID 26437031

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

Detection of karyotypic aberrations in acute myeloblastic leukaemia: a prospective comparison between PCR/FISH and standard cytogenetics in 140 patients with de novo AML.

Krauter J, Peter W, Pascheberg U, Heinze B, Bergmann L, Hoelzer D, Lübbert M, Schlimok G, Arnold R, Kirchner H, Port M, Ganser A

Br J Haematol. 1998 Oct;103(1):72-8

PMID 9792292

Cytogenetic studies of leukemic recurrence in recipients of bone marrow allografts.

Lawler SD, Khokhar MT, Davies H, Williams GJ, Powles R.

Cancer Genet Cytogenet. 1990 Jul 15;47(2):249-63.

PMID 2357698

Clinical and genetic features of pediatric acute lymphoblastic leukemia in Down syndrome in the Nordic countries.

Lundin C, Forestier E, Klarskov Andersen M, Autio K, Barbany G, Cavelier L, Golovleva I, Heim S, Heinonen K, Hovland R, Johannsson JH, Kjeldsen E,Nordgren A, Palmqvist L, Johansson B; Nordic Society of Pediatric Hematology Oncology (NOPHO); Swedish Cytogenetic Leukemia Study Group (SCLSG);NOPHO Leukemia Cytogenetic Study Group (NLCSG)

J Hematol Oncol. 2014 Apr 11;7:32. doi: 10.1186/1756-8722-7-32.

PMID 24726034

Mitelman Database of Chromosome Aberration in Cancer

Mitelman F, Johansson B, Mertens F

https://cgap.nci.nih.gov/

Telomerase activity and cytogenetic changes in chronic myeloid leukemia with disease progression.

Ohyashiki K, Ohyashiki JH, Iwama H, Hayashi S, Shay JW, Toyama K.

Leukemia. 1997 Feb;11(2):190-4

PMID 9009079

Chromosomes and causation of human cancer and leukemia. XXVI. Banding studies in acute lymphoblastic leukemia (ALL).

Oshimura M, Freeman AI, Sandberg AA.

Cancer. 1977 Sep;40(3):1161-72

PMID  268996

High concordance of subtypes of childhood acute lymphoblastic leukemia within families: lessons from sibships with multiple cases of leukemia.

Schmiegelow K, Lausten Thomsen U, Baruchel A, Pacheco CE, Pieters R, Pombo-de-Oliveira MS, Andersen EW, Rostgaard K, Hjalgrim H, Pui CH

Leukemia. 2012 Apr;26(4):675-81. doi: 10.1038/leu.2011.274. Epub 2011 Oct 18.

PMID 22005784

Acute lymphoblastic leukemia in elderly patients: a single institution's experience.

Shin DY, Kim I, Kim KH, Choi Y, Beom SH, Yang Y, Lim Y, Lee E, Lee JK, Kim JY, Kim HK, Yoon SS, Lee DS, Park S, Kim BK.

Korean J Intern Med. 2011 Sep;26(3):328-39. doi: 10.3904/kjim.2011.26.3.328. Epub 2011 Sep 13

PMID 22016594

Amplification of band q22 of chromosome 21, including AML1, in older children with acute lymphoblastic leukemia: an emerging molecular cytogenetic subgroup.

Soulier J, Trakhtenbrot L, Najfeld V, Lipton JM, Mathew S, Avet-Loiseau H, De Braekeleer M, Salem S, Baruchel A, Raimondi SC, Raynaud SD.

Leukemia. 2003 Aug;17(8):1679-82.

PMID 12886264

DNA methylation of membrane-bound tyrosine phosphatase genes in acute lymphoblastic leukaemia.

Stevenson WS, Best OG, Przybylla A, Chen Q, Singh N, Koleth M, Pierce S, Kennedy T, Tong W, Kuang SQ, Garcia-Manero G.

Leukemia. 2014 Apr;28(4):787-93. doi: 10.1038/leu.2013.270. Epub 2013 Sep 18.

PMID 24045499

Chromosome 20q deletion: a recurrent cytogenetic abnormality in patients with chronic myelogenous leukemia in remission.

Sun J, Yin CC, Cui W, Chen SS, Medeiros LJ, Lu G.

Am J Clin Pathol. 2011 Mar;135(3):391-7. doi: 10.1309/AJCPQFSC9ZJNMAZ6

PMID 21350093

A single split-signal FISH probe set allows detection of TAL1 translocations as well as SIL-TAL1 fusion genes in a single test.

van der Burg M, Smit B, Brinkhof B, Barendregt BH, Verschuren MC, Dib M, Beverloo HB, van Dongen JJ, Langerak AW.

Leukemia. 2002 Apr;16(4):755-61.

PMID  11960364

Citation

This paper should be referenced as such :

Lubomir Mitev, Lilya Grachlyova, Aselina Asenova

del(18)(p11)

Atlas Genet Cytogenet Oncol Haematol. 2017;21(12):443-446.

Free journal version : [ pdf ]   [ DOI ]

On line version : http://AtlasGeneticsOncology.org/Anomalies/del18p11ID1314.html

External links

arrayMap (UZH-SIB Zurich)	Morph ( 9873/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)	Morph ( 9874/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)	Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)	Morph ( 9975/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)	Morph ( 9989/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)	Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)	Morph ( 9837/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)	Morph ( 9690/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]

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