t(2;5)(p23;q35) SQSTM1/ALK

2011-11-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Phenotype stem cell origin

One case to date, a 67-year-old male patient (Takeuchi et al., 2011).

Cytology

Anti-ALK immunohistochemistry showed a diffuse cytoplasmic staining pattern, in contrast with the nuclear and cytoplasmic pattern usually sen in the NPM1-ALK fusion gene/protein.

Prognosis

Complete remission was obtained, but the patient relapsed four months later.

Genes Involved and Proteins

Gene name
ALK (anaplastic lymphoma receptor tyrosine kinase)
Location
2p23.2
Protein description
ALK is composed of an extracellular region (containing two MAM (meprin, A-5 protein, and receptor protein-tyrosine phosphatase mu) and one LDLa (low-density lipoprotein receptor) domains, and one glycin-rich region), a transmembrane domain, and an intracellular region (composed of a tyrosine kinase domain. Membrane receptor tyrosine kinase.
Germinal mutations
In familial neuroblastoma.
Somatic mutations
Fusion proteins in anaplastic large cell lymphoma, some diffuse large B-cell lymphomas, inflammatory myofibroblastic tumours, and some non-small cell lung cancers. Somatic mutations in sporadic neuroblastoma (review in Allouche, 2010).
Gene name
SQSTM1 (sequestosome 1)
Location
5q35.3
Protein description
SQSTM1 (sequestosome1), also called p62, is a scaffolding protein with several interaction domains; it is composed of an OPR domain (octicosapeptide repeat (PB1 dimerization domain)), a Zn finger, a LIM protein-binding region, a TRAF6-binding motif, a PEST sequence (proline, glutamic acid, serine, and threonine rich), a LIR motif (LC3 interaction region, SGGDDDWTHLSS), a second PEST sequence, a KIR (keap1 interacting region), and an UBA (ubiquitin-associated) domain. Interacts with Caspase-8 and the apoptosis, machinery, MAPK kinases such as MAP2K5 (15q23), LCK (1p34), NBR1 (17q21), PRKCI (3q26), PAWR (12q21), RIPK1 (6p25), TRAF6 (11p12) and NTRK1 (1q23) and the NF-kappaB pathway, KEAP1 (19p13), GABARAPL1 (12p13), MAP1LC3A/LC3 (20q11), and ubiquitin. Mediates the interaction between TRAF6 and CYLD (16q12). Implicated in the activation of the transcription factor NF-kappaB. Involved in the autophagy-lysosome pathway. Plays a role in the formation of cytoplasmic proteinaceous inclusions in various pathologic situations where autophagy is inactivated (Geetha and Wooten, 2002; Lamark et al., 2009; Moscat and Diaz-Meco, 2009; Moscat et al., 2009; Ichimura and Komatsu, 2010; Komatsu and Ichimura, 2010; Moscat and Diaz-Meco, 2011).
Germinal mutations
Mutated in Pagets disease of bone.

Result of the Chromosomal Anomaly

Description

Exon 5 of SQSTM1 fused to the ALK exon 20.
Atlas Image

Description

Fuses the PB1 dimerization domain of SQSTM1 to the tyrosine kinase domain of ALK, resulting in a constitutive activation of the ALK kinase domain.

Bibliography

Pubmed IDLast YearTitleAuthors
118520442002Structure and functional properties of the ubiquitin binding protein p62.Geetha T et al
208147912010Selective degradation of p62 by autophagy.Ichimura Y et al
201533262010Physiological significance of selective degradation of p62 by autophagy.Komatsu M et al
195027942009NBR1 and p62 as cargo receptors for selective autophagy of ubiquitinated targets.Lamark T et al
220788742011Feedback on fat: p62-mTORC1-autophagy connections.Moscat J et al
197139722009Of the atypical PKCs, Par-4 and p62: recent understandings of the biology and pathology of a PB1-dominated complex.Moscat J et al
211349802011Identification of a novel fusion, SQSTM1-ALK, in ALK-positive large B-cell lymphoma.Takeuchi K et al

Summary

Fusion gene

SQSTM1/ALK SQSTM1 (5q35.3) ALK (2p23.2) COF 1051 1052|SQSTM1/ALK SQSTM1 (5q35.3) ALK (2p23.2) M t(2;5)(p23;q35)|SQSTM1/ALK SQSTM1 (5q35.3) ALK (2p23.2) TIC

Note

Not to be confused with the t(2;5)(p23;q35) with NPM1-ALK involvement.

Citation

Jean-Loup Huret

t(2;5)(p23;q35) SQSTM1/ALK

Atlas Genet Cytogenet Oncol Haematol. 2011-11-01

Online version: http://atlasgeneticsoncology.org/haematological/1584/t(2;5)(p23;q35)

External Links