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t(11;14)(p15;q22) AP2A2/NID2

Written2014-08Nathalie Douet-Guilbert, Etienne De Braekeleer, Corinne Tous, Nadia Guéganic, Audrey Basinko, Marie-Josée Le Bris, Frédéric Morel, Marc De Braekeleer
Cytogenetics Laboratory, Faculty of Medicine, University of Brest, France

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ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id 1677

Clinics and Pathology

Disease Myelodysplastic syndrome
Epidemiology A single case of Philadelphia chromosome-positive chronic myeloid leukemia with t(11;14)(p15;q22) following allogeneic stem cell transplantation in a 32 year-old male is reported in the literature. The translocation is associated with a complex karyotype. No molecular characterization was performed (Karrman et al., 2007).
Clinics A 71-year-old woman seen because of macrocytic anemia without etiology.
Cytology Bone marrow aspirate showing dysgranulopoiesis and dyserythropoiesis. Presence of ring sideroblasts (24%) signing a refractory anemia with ring sideroblasts (RARS).
Evolution Patient alive two years later.


Note The t(11;14)(p15;q22) involves two genes, the AP2A2 and NID2 genes, that have never been shown to form a fusion gene.
Cytogenetics Morphological t(11;14)(p15;q22) is identified by banding cytogenetics.
  RHG banding showing chromosomes 11 and 14 and the derivatives der(11) and der(14).
Cytogenetics Molecular To determine the position of the breakpoints on chromosomes 11 and 14, BACs located in the bands of interest were used as probes in FISH experiments. Analysis with RP11-51L17 showed that one signal hybridized to the normal chromosome 11, and the other hybridized to the der(14). Analysis with RP11-963I11 showed that one signal hybridized to the normal chromosome 14, and the other split and hybridized to both der(11) and der(14). Co-hybridization with both BAC clones showed one fusion signal. RP11-51L17 contains the AP2A2 (adaptor-related protein complex 2, alpha 2 subunit) gene and RP11-963I11 the NID2 (Nidogen 2) gene.
  FISH with BACs RP11-51L17 (spectrum orange, located in 11p15 and containing AP2A2) and RP11-963I11 (spectrum green, located in 14q22 and containing NID2) showing co-hybridization. During the FISH analyses with BAC clones on chromosome 11, we found that RP11-51L17 was translocated to der(14) and RP11-613G2 was deleted. RP11-51L17 is mapped between positions 774448 and 952590 and RP11-613G2 between positions 952562 and 1128625. The AP2A2 is mapped from positions 925809 to 1012245. The region of overlap between both BAC clones is included between exons 1 and 2 of AP2A2 (UCSC Genome Browser on Human Feb. 2009 (GRCh37/hg19) Assembly). Deletion of RP11-613G2 explains why only one fusion signal was observed.

Genes involved and Proteins

Gene NameAP2A2 (adaptor related protein complex 2 alpha 2 subunit)
Location 11p15.5
Dna / Rna The AP2A2 gene contains 22 coding exons, spanning 86.4 kb. Three alternative transcripts are known (Nagase et al., 1998).
Protein The protein has 939 amino acids. It is a component of the adaptor protein complex 2 (AP-2) (Ohno, 2006). AP-2 is involved in clathrin-dependent endocytosis in which proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles) which are destined for fusion with the early endosome. AP-2 is involved in a wide range of biological processes, notably signalling mediated by Notch, Wnt, EGF and transforming growth factor-b (TGF-b) superfamily members (Foerster et al., 2013; Mizutani et al., 2010; Sorkin and von Zastrow, 2009; Yao et al., 2002; Yu et al., 2007). AP2 was also found to be essential for thrombopoietin (Tpo)-stimulated clathrin-mediated internalization of its receptor c-Mpl. As Tpo promotes proliferation and survival of hematopoietic stem and progenitor cells and regulates megakaryocyte lineage differentiation and maturation, Tpo signal transduction has to be controlled (Hitchcock et al., 2008). More recently, a role for AP2A2 has been suggested in asymmetric cell division and self-renewal of hematopoietic stem and progenitor cells (Ting et al., 2012).
Gene NameNID2 (nidogen 2)
Location 14q22.1
Note NID2 expression was shown to be downregulated in tumor tissues from patients with hepatocellular carcinoma (Cheng et al., 2012). Aberrant methylation of NID2 promoter induces loss of gene expression in gastrointestinal tumors (stomach and colon) and in oral squamous cell carcinoma (Guerrero-Preston et al., 2011; Ulazzi et al., 2007).
Dna / Rna The NID2 gene contains 21 coding exons, spanning 64.4 kb (Kohfeldt et al., 1998).
Protein The NID2 gene encodes a 1375 amino acids protein that is a member of the nidogen family of basement membranes that control diverse cellular activities, including adhesion, migration, differentiation, gene expression and apoptosis. Its three dimensional structure consists of three globular domains connected by a flexible link and a rod (Kohfeldt et al., 1998). Disruption of the integrity of the basement membrane creates an invasion-permissive environment, often promoting cancer cell proliferation and invasion (metastasis) (Lester and McCarthy, 1992).

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.


Clinical significance of decreased nidogen-2 expression in the tumor tissue and serum of patients with hepatocellular carcinoma.
Cheng ZX, Huang XH, Wang Q, Chen JS, Zhang LJ, Chen XL.
J Surg Oncol. 2012 Jan;105(1):71-80. doi: 10.1002/jso.22047. Epub 2011 Aug 3.
PMID 21815147
Characterization of the EGFR interactome reveals associated protein complex networks and intracellular receptor dynamics.
Foerster S, Kacprowski T, Dhople VM, Hammer E, Herzog S, Saafan H, Bien-Moller S, Albrecht M, Volker U, Ritter CA.
Proteomics. 2013 Nov;13(21):3131-44. doi: 10.1002/pmic.201300154. Epub 2013 Oct 1.
PMID 23956138
NID2 and HOXA9 promoter hypermethylation as biomarkers for prevention and early detection in oral cavity squamous cell carcinoma tissues and saliva.
Guerrero-Preston R, Soudry E, Acero J, Orera M, Moreno-Lopez L, Macia-Colon G, Jaffe A, Berdasco M, Ili-Gangas C, Brebi-Mieville P, Fu Y, Engstrom C, Irizarry RA, Esteller M, Westra W, Koch W, Califano J, Sidransky D.
Cancer Prev Res (Phila). 2011 Jul;4(7):1061-72. doi: 10.1158/1940-6207.CAPR-11-0006. Epub 2011 May 10.
PMID 21558411
YRRL motifs in the cytoplasmic domain of the thrombopoietin receptor regulate receptor internalization and degradation.
Hitchcock IS, Chen MM, King JR, Kaushansky K.
Blood. 2008 Sep 15;112(6):2222-31. doi: 10.1182/blood-2008-01-134049. Epub 2008 May 16.
PMID 18487512
Cytogenetic evolution patterns in CML post-SCT.
Karrman K, Sallerfors B, Lenhoff S, Fioretos T, Johansson B.
Bone Marrow Transplant. 2007 Feb;39(3):165-71. Epub 2007 Jan 8.
PMID 17211433
Nidogen-2: a new basement membrane protein with diverse binding properties.
Kohfeldt E, Sasaki T, Gohring W, Timpl R.
J Mol Biol. 1998 Sep 11;282(1):99-109.
PMID 9733643
Tumor cell adhesion to the extracellular matrix and signal transduction mechanisms implicated in tumor cell motility, invasion and metastasis.
Lester BR, McCarthy JB.
Cancer Metastasis Rev. 1992 Mar;11(1):31-44. (REVIEW)
PMID 1511495
Arkadia complexes with clathrin adaptor AP2 and regulates EGF signalling.
Mizutani A, Saitoh M, Imamura T, Miyazawa K, Miyazono K.
J Biochem. 2010 Dec;148(6):733-41. doi: 10.1093/jb/mvq127. Epub 2010 Oct 21.
PMID 20965945
Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.
Nagase T, Ishikawa K, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O.
DNA Res. 1998 Feb 28;5(1):31-9.
PMID 9628581
Clathrin-associated adaptor protein complexes.
Ohno H.
J Cell Sci. 2006 Sep 15;119(Pt 18):3719-21.
PMID 16959901
Endocytosis and signalling: intertwining molecular networks.
Sorkin A, von Zastrow M.
Nat Rev Mol Cell Biol. 2009 Sep;10(9):609-22. doi: 10.1038/nrm2748. (REVIEW)
PMID 19696798
Asymmetric segregation and self-renewal of hematopoietic stem and progenitor cells with endocytic Ap2a2.
Ting SB, Deneault E, Hope K, Cellot S, Chagraoui J, Mayotte N, Dorn JF, Laverdure JP, Harvey M, Hawkins ED, Russell SM, Maddox PS, Iscove NN, Sauvageau G.
Blood. 2012 Mar 15;119(11):2510-22. doi: 10.1182/blood-2011-11-393272. Epub 2011 Dec 14.
PMID 22174158
Nidogen 1 and 2 gene promoters are aberrantly methylated in human gastrointestinal cancer.
Ulazzi L, Sabbioni S, Miotto E, Veronese A, Angusti A, Gafa R, Manfredini S, Farinati F, Sasaki T, Lanza G, Negrini M.
Mol Cancer. 2007 Feb 28;6:17.
PMID 17328794
Transforming growth factor-beta receptors interact with AP2 by direct binding to beta2 subunit.
Yao D, Ehrlich M, Henis YI, Leof EB.
Mol Biol Cell. 2002 Nov;13(11):4001-12.
PMID 12429842
Association of Dishevelled with the clathrin AP-2 adaptor is required for Frizzled endocytosis and planar cell polarity signaling.
Yu A, Rual JF, Tamai K, Harada Y, Vidal M, He X, Kirchhausen T.
Dev Cell. 2007 Jan;12(1):129-41.
PMID 17199046


This paper should be referenced as such :
N Douet-Guilbert, Braekeleer E De, C Tous, N Guéganic, A Basinko, Bris MJ Le, F Morel, Braekeleer M De
t(11;14)(p15;q22) AP2A2/NID2
Atlas Genet Cytogenet Oncol Haematol. 2015;19(3):227-229.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 t(11;14)(p15;q22) AP2A2/NID2

External links

Mitelman databaset(11;14)(p15;q22)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9989/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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