Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

LPP (lipoma preferred partner)

Written2004-05Marleen M Petit
Laboratory for Molecular Oncology, Department of Human Genetics, University of Leuven (K.U.Leuven) & VIB, Herestraat 49, B-3000 Leuven, Belgium

(Note : for Links provided by Atlas : click)

Identity

Other alias
LocusID (NCBI) 4026
Atlas_Id 72
Location 3q28  [Link to chromosome band 3q28]
Location_base_pair Starts at and ends at bp from pter
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
DLG1 (3q29) / LPP (3q28)DMD (Xp21.2) / LPP (3q28)FAM19A3 (1p13.2) / LPP (3q28)
HMGA2 (12q14.3) / LPP (3q28)KMT2A (11q23.3) / LPP (3q28)LPP (3q28) / ABHD17C (15q25.1)
LPP (3q28) / ADGRL3 (4q13.1)LPP (3q28) / BCL6 (3q27.3)LPP (3q28) / CASR (3q13.33)
LPP (3q28) / CASR (3q21.1)LPP (3q28) / CD58 (1p13.1)LPP (3q28) / CHSY1 (15q26.3)
LPP (3q28) / CLSTN2 (3q23)LPP (3q28) / F2 (11p11.2)LPP (3q28) / GNL2 (1p34.3)
LPP (3q28) / GOLIM4 (3q26.2)LPP (3q28) / HMGA2 (12q14.3)LPP (3q28) / KMT2A (11q23.3)
LPP (3q28) / LPP (3q28)LPP (3q28) / LSM1 (8p11.23)LPP (3q28) / P3H2 (3q28)
LPP (3q28) / SPATA16 (3q26.31)LPP (3q28) / SSU72 (1p36.33)LPP (3q28) / ST6GAL1 (3q27.3)
LPP (3q28) / TP63 (3q28)LPP (3q28) / UBE2R2 (9p13.3)NCKIPSD (3p21.31) / LPP (3q28)
SEPT9 (17q25.2) / LPP (3q28)SEPT9 (17q25.3) / LPP (3q28)SFTPB (2p11.2) / LPP (3q28)
TAGLN2 (1q23.2) / LPP (3q28)TC2N (14q32.12) / LPP (3q28)

DNA/RNA

 
Description At least 11 exons; predicted start codon in exon 3, stop codon in exon 11; the protein coding region is covered by the overlapping "CEPH Mark 1" YAC clones 135H6 and 192B10 (start codon in 135H6, stop codon in 192B10) and is dispersed over at least 400 kb genomic DNA; the LIM domains are encoded by separate exons: LIM 1 is encoded by exon 8, LIM 2 by exon 9, and LIM 3 by exon 10 and part of exon 11.
Transcription mRNA: ubiquitously: > 10 kb; testis: additional transcripts of 1.8 kb and 1.25 kb
Pseudogene no pseudogenes

Protein

Description 612 amino acids; proline-rich region (amino-terminal 2/3 of the protein) followed by three LIM domains (carboxy-terminal 1/3 of the protein). Proline-rich region contains an alfa-actinin binding site, two VASP-binding motifs, and a nuclear export signal.
Expression Smooth muscle marker; readily detected on Western blot with an LPP-antibody in all fibroblastic and epithelial cell lines tested to date.
Localisation LPP is present in the cytoplasm of cells as well as at sites of cell adhesion such as focal adhesions (attachments sites to the extracellular matrix) and cell-cell contacts; LPP also shuttles to the nucleus and its nuclear-cytoplasmic localisation is regulated in part by a nuclear export signal (NES) which is sensitive to the drug leptomycin B.
Function Because of their structural features (many protein-protein interaction domains) and their characteristic to shuttle between the nucleus and the cytoplasm, LPP and its family members (see below) have been proposed to be scaffolding proteins involved in signal transduction from sites of cell adhesion to the nucleus; LPP has been shown to harbour transcriptional activation capacity in luciferase reporter assays, suggesting that LPP may be directly involved in the regulation of gene expression; LPP was found to be highly expressed in smooth muscle, and a role for LPP in regulating cell motility was proposed; the precise function of LPP remains to be elucidated.
Homology LPP is a member of the zyxin family of proteins, which contains five members: ajuba, LIMD1, LPP, TRIP6 and zyxin. The family hallmark of these proteins are three clustered LIM domains at the carboxy-terminus, which are protein interaction domains. All family members are present at sites of cell adhesion and have the ability to shuttle to the nucleus, and all family members have one or more nuclear export signals.

Mutations

Somatic HMGA2/LPP fusion proteins and MLL/LPP fusion proteins (Fig2).

Implicated in

Note
  
Entity solitary lipomas
Disease Benign tumors of adipose tissue.
Prognosis Can be surgically removed with no recurrence in most cases.
Cytogenetics More than 60% of solitary lipomas have an aberrant karyotype; 2/3 of these carry 12q15 rearrangements, most often translocations, affecting the HMGA2 gene; 1/4 of the latter have chromosomal region 3q27-q28 (containing LPP) as 12q15 translocation partner as such creating an HMGA2/LPP fusion gene.
Hybrid/Mutated Gene HMGA2/LPP hybrid gene containing the first three exons of HMGA2 and exons 8-11 or 9-11 of LPP; under the regulation of the HMGA2 promoter.
Abnormal Protein HMGA2/LPP fusion transcripts encode the three DNA-binding domains of HMGA2 followed by two LIM domains (LIM 2 and LIM 3) or a portion of the proline-rich region and all three LIM domains of LPP.
 
  
  
Entity Pulmonary chondroid hamartomas
Disease Benign mesenchymal tumors of the lung.
Prognosis good
Cytogenetics More than 70% of pulmonary chondroid hamartomas have an aberrant karyotype; 70% of these carry 12q15 rearrangements, most often translocations, affecting the HMGA2 gene; 1/8 of the latter have chromosomal region 3q27-q28 (containing LPP) as 12q15 translocation partner as such creating an HMGA2/LPP fusion gene.
Hybrid/Mutated Gene HMGA2/LPP hybrid gene containing the first three exons of HMGA2 and exons 9-11 of LPP; under the regulation of the HMGA2 promoter.
Abnormal Protein HMGA2/LPP fusion transcripts encode the three DNA-binding domains of HMGA2 followed by the two most carboxy-terminal LIM domains (LIM 2 and LIM 3) of LPP.
  
  
Entity Parosteal lipoma
Disease Rare deep-seated benign tumor of adipose tissue comprising less than 0.5% of all lipomas; parosteal lipomas exhibit a contiguous relationship with the periostium; because of their intimate relationship to the bone, they are considered as lipomas of bone.
Prognosis Most often asymptomatic; in some cases: loss of motor and/or sensory function as a result of the compression or stretching of a nerve.
Cytogenetics One case reported with rearrangement of LPP t(3;12)(q28;q14).
Hybrid/Mutated Gene HMGA2/LPP hybrid gene containing the first three exons of HMGA2 and exons 9-11 of LPP; under the regulation of the HMGA2 promoter.
Abnormal Protein HMGA2/LPP fusion transcripts encode the three DNA-binding domains of HMGA2 followed by the two most carboxy-terminal LIM domains (LIM 2 and LIM 3) of LPP.
  
  
Entity Soft tissue chondroma
Disease Benign tumor of cartilage; rare entity.
Cytogenetics Only 31 cases with abnormal karyotypes have been reported (11-2003); 12q15 nonrandomly involved; one case reported with rearrangement of LPP t(3;12)(q27;q15).
Hybrid/Mutated Gene HMGA2/LPP hybrid gene containing the first three exons of HMGA2 and exons 9-11 of LPP; under the regulation of the HMGA2 promoter.
Abnormal Protein HMGA2/LPP fusion transcripts encode the three DNA-binding domains of HMGA2 followed by the two most carboxy-terminal LIM domains (LIM 2 and LIM 3) of LPP.
  
  
Entity AML-M5
Disease Secondary leukemia following treatment with DNA topoisomerase II inhibitors.
Cytogenetics MLL gene on 11q23 frequently involved; one case reported with rearrangement of LPP t(3;11)(q28;q23).
Hybrid/Mutated Gene MLL/LPP hybrid gene containing the first 8 exons of MLL and exons 9-11 of LPP; under the regulation of the MLL promoter.
Abnormal Protein MLL/LPP fusion transcripts encode the three DNA-binding domains and the methyltransferase-like domain of MLL followed by the two most carboxy-terminal LIM domains (LIM 2 and LIM 3) of LPP.
  

Breakpoints

 

Bibliography

Human LPP gene is fused to MLL in a secondary acute leukemia with a t(3;11) (q28;q23).
Dahéron L, Veinstein A, Brizard F, Drabkin H, Lacotte L, Guilhot F, Larsen CJ, Brizard A, Roche J
Genes, chromosomes & cancer. 2001 ; 31 (4) : 382-389.
PMID 11433529
 
Fusion, disruption, and expression of HMGA2 in bone and soft tissue chondromas.
Dahlén A, Mertens F, Rydholm A, Brosjö O, Wejde J, Mandahl N, Panagopoulos I
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2003 ; 16 (11) : 1132-1140.
PMID 14614053
 
LPP, a LIM protein highly expressed in smooth muscle.
Gorenne I, Nakamoto RK, Phelps CP, Beckerle MC, Somlyo AV, Somlyo AP
American journal of physiology. Cell physiology. 2003 ; 285 (3) : C674-C685.
PMID 12760907
 
A novel LPP fusion gene indicates the crucial role of truncated LPP proteins in lipomas and pulmonary chondroid hamartomas.
Lemke I, Rogalla P, Bullerdiek J
Cytogenetics and cell genetics. 2001 ; 95 (3-4) : 153-156.
PMID 12063392
 
The lipoma preferred partner LPP interacts with alpha-actinin.
Li B, Zhuang L, Reinhard M, Trueb B
Journal of cell science. 2003 ; 116 (Pt 7) : 1359-1366.
PMID 12615977
 
Prediction of cell type-specific gene modules: identification and initial characterization of a core set of smooth muscle-specific genes.
Nelander S, Mostad P, Lindahl P
Genome research. 2003 ; 13 (8) : 1838-1854.
PMID 12869577
 
LPP, an actin cytoskeleton protein related to zyxin, harbors a nuclear export signal and transcriptional activation capacity.
Petit MM, Fradelizi J, Golsteyn RM, Ayoubi TA, Menichi B, Louvard D, Van de Ven WJ, Friederich E
Molecular biology of the cell. 2000 ; 11 (1) : 117-129.
PMID 10637295
 
The focal adhesion and nuclear targeting capacity of the LIM-containing lipoma-preferred partner (LPP) protein.
Petit MM, Meulemans SM, Van de Ven WJ
The Journal of biological chemistry. 2003 ; 278 (4) : 2157-2168.
PMID 12441356
 
LPP, the preferred fusion partner gene of HMGIC in lipomas, is a novel member of the LIM protein gene family.
Petit MM, Mols R, Schoenmakers EF, Mandahl N, Van de Ven WJ
Genomics. 1996 ; 36 (1) : 118-129.
PMID 8812423
 
Expression of reciprocal fusion transcripts of the HMGIC and LPP genes in parosteal lipoma.
Petit MM, Swarts S, Bridge JA, Van de Ven WJ
Cancer genetics and cytogenetics. 1998 ; 106 (1) : 18-23.
PMID 9772904
 
The t(3;12)(q27;q14-q15) with underlying HMGIC-LPP fusion is not determining an adipocytic phenotype.
Rogalla P, Kazmierczak B, Meyer-Bolte K, Tran KH, Bullerdiek J
Genes, chromosomes & cancer. 1998 ; 22 (2) : 100-104.
PMID 9598796
 

Citation

This paper should be referenced as such :
Petit, MM
LPP (lipoma preferred partner)
Atlas Genet Cytogenet Oncol Haematol. 2004;8(3):193-197.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/LPPID72.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 6 ]
  t(3;11)(q28;q23) KMT2A/LPP
del(3)(q27):del(3)(q27q28) LPP/BCL6
del(3)(q27q28) LPP/BCL6
t(3;11)(q28;q23) KMT2A/LPP
del(3)(q27):del(3)(q27q28) LPP/BCL6
del(3)(q27q28) LPP/BCL6


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 14 ]
  Bone: Soft tissue chondroma with t(3;12)(q27;q15) HMGA2/LPP
Soft Tissues: Ordinary lipoma with t(1;12)(p32;q14) HMGA2/PPAP2B
Lung: Translocations in Small Cell Carcinoma
Lung: Translocations in Squamous Cell Carcinoma
del(3)(q28q28) LPP/TPRG1
t(1;3)(p13;q28) FAM19A3/LPP
t(3;3)(q26;q28) LPP/GOLIM4
t(3;3)(q26;q28) LPP/SPATA16
t(3;3)(q27;q28) LPP/ST6GAL1
t(3;11)(q28;p11) LPP/F2
t(3;12)(q28;q14) HMGA2/LPP
t(3;14)(q28;q32) TC2N/LPP
t(3;15)(q28;q25) LPP/ABHD17C
t(3;17)(q28;q25) SEPT9/LPP


External links

Nomenclature
Cards
AtlasLPPID72.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)4026
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Oct 18 17:41:41 CEST 2018

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.