Download Leukaemia Section t(11;14)(p15;q22) AP2A2/NID2 Atlas of Genetics and Cytogenetics in Oncology and Haematology

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
INIST-CNRS
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Leukaemia Section
Short Communication
t(11;14)(p15;q22) AP2A2/NID2
Nathalie 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 (NDG, EDB, CT, NG, AB,
MJLB, FM, MDB)
Published in Atlas Database: August 2014
Online updated version : http://AtlasGeneticsOncology.org/Anomalies/t1114p15q22ID1677.html
DOI: 10.4267/2042/56417
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2015 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Abstract
Review on t(11;14)(p15;q22) AP2A2/NID2, with
data on clinics, and the genes implicated.
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).
RHG banding showing chromosomes 11 and 14 and the
derivatives der(11) and der(14).
Clinics
Cytogenetics morphological
A 71-year-old woman seen because of macrocytic
anemia without etiology.
t(11;14)(p15;q22)
cytogenetics.
Cytology
identified
by
banding
Cytogenetics molecular
Bone marrow aspirate showing dysgranulopoiesis
and dyserythropoiesis.
Presence of ring sideroblasts (24%) signing a
refractory anemia with ring sideroblasts (RARS).
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.
Evolution
Patient alive two years later.
Cytogenetics
The t(11;14)(p15;q22) involves two genes, the
AP2A2 and NID2 genes, that have never been
shown to form a fusion gene.
Atlas Genet Cytogenet Oncol Haematol. 2015; 19(3)
is
227
t(11;14)(p15;q22) AP2A2/NID2
Douet-Guilbert N, et al.
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.
RP11-51L17 contains the AP2A2 (adaptor-related
protein complex 2, alpha 2 subunit) gene and RP11963I11 the NID2 (Nidogen 2) gene.
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
Genes involved and
proteins
AP2A2
Location
11p15.5
Atlas Genet Cytogenet Oncol Haematol. 2015; 19(3)
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t(11;14)(p15;q22) AP2A2/NID2
Douet-Guilbert N, et al.
Nomura N, Ohara O. 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. DNA Res. 1998 Feb 28;5(1):31-9
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).
Yao D, Ehrlich M, Henis YI, Leof EB. Transforming growth
factor-beta receptors interact with AP2 by direct binding to
beta2 subunit. Mol Biol Cell. 2002 Nov;13(11):4001-12
Ohno H. Clathrin-associated adaptor protein complexes. J
Cell Sci. 2006 Sep 15;119(Pt 18):3719-21
Karrman K, Sallerfors B, Lenhoff S, Fioretos T, Johansson
B. Cytogenetic evolution patterns in CML post-SCT. Bone
Marrow Transplant. 2007 Feb;39(3):165-71
Ulazzi L, Sabbioni S, Miotto E, Veronese A, Angusti A,
Gafà R, Manfredini S, Farinati F, Sasaki T, Lanza G,
Negrini M. Nidogen 1 and 2 gene promoters are aberrantly
methylated in human gastrointestinal cancer. Mol Cancer.
2007 Feb 28;6:17
Yu A, Rual JF, Tamai K, Harada Y, Vidal M, He X,
Kirchhausen T. Association of Dishevelled with the clathrin
AP-2 adaptor is required for Frizzled endocytosis and
planar cell polarity signaling. Dev Cell. 2007
Jan;12(1):129-41
NID2
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).
Hitchcock IS, Chen MM, King JR, Kaushansky K. YRRL
motifs in the cytoplasmic domain of the thrombopoietin
receptor regulate receptor internalization and degradation.
Blood. 2008 Sep 15;112(6):2222-31
Sorkin A, von Zastrow M. Endocytosis and signalling:
intertwining molecular networks. Nat Rev Mol Cell Biol.
2009 Sep;10(9):609-22
Mizutani A, Saitoh M, Imamura T, Miyazawa K, Miyazono
K. Arkadia complexes with clathrin adaptor AP2 and
regulates
EGF
signalling.
J
Biochem.
2010
Dec;148(6):733-41
Guerrero-Preston R, Soudry E, Acero J, Orera M, MorenoLópez L, Macía-Colón 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. NID2 and
HOXA9 promoter hypermethylation as biomarkers for
prevention and early detection in oral cavity squamous cell
carcinoma tissues and saliva. Cancer Prev Res (Phila).
2011 Jul;4(7):1061-72
Cheng ZX, Huang XH, Wang Q, Chen JS, Zhang LJ, Chen
XL. Clinical significance of decreased nidogen-2
expression in the tumor tissue and serum of patients with
hepatocellular carcinoma. J Surg Oncol. 2012
Jan;105(1):71-80
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.
Asymmetric segregation and self-renewal of hematopoietic
stem and progenitor cells with endocytic Ap2a2. Blood.
2012 Mar 15;119(11):2510-22
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This article should be referenced as such:
Kohfeldt E, Sasaki T, Göhring W, Timpl R. Nidogen-2: a
new basement membrane protein with diverse binding
properties. J Mol Biol. 1998 Sep 11;282(1):99-109
Douet-Guilbert N, De Braekeleer E, Tous C, Guéganic N,
Basinko A, Le Bris MJ, Morel F, De Braekeleer M.
t(11;14)(p15;q22) AP2A2/NID2. Atlas Genet Cytogenet
Oncol Haematol. 2015; 19(3):227-229.
Nagase T, Ishikawa K, Miyajima N, Tanaka A, Kotani H,
Atlas Genet Cytogenet Oncol Haematol. 2015; 19(3)
229