t(6;14)(p22;q32) IGH/ID4

2008-04-01   Jean-Loup Huret 

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

Clinics and Pathology

Disease

B-cell acute lymphoblastic leukaemia (B-ALL)

Phenotype stem cell origin

Pre-B ALL: CD10+ in 14 of 15 cases, CD19+ probably in the remaining case.

Epidemiology

15 cases available: 9 male and 6 female patients; mediane age was 16 years (range: 6 - 48 years).

Clinics

Complete remission was obtained in 15 of 15 cases.
Atlas Image

Prognosis

Prognosis looks fair (see survival curve).

Genes Involved and Proteins

Note
Deletion of CDKN2A and PAX5 was found in 10 of 10 cases tested, eventhough in cases without isochromosome (9q)
Gene name
ID4 (inhibitor of DNA binding 4, dominant negative helix-loop-helix protein)
Location
6p22.3
Protein description
Member of the ID gene family : "Inhibitors of DNA binding". They are transcription factors which act as transcription inhibitory proteins. They are basic helix-loop-helix (bHLH) proteins which contain the bHLH dimerization domain, but lack the DNA binding domain. They form heterodimers with other bHLH proteins and inhibit them. ID4 may play an important suppressive role in tumor progression, and its silencing by hypermethylation favours tumorogenesis
Gene name
IGH (Immunoglobulin Heavy)
Location
14q32.33

Result of the Chromosomal Anomaly

Description

No hybrid gene, but juxtaposition of ID4 to the IGH enhancer, leading to ID4 overexpression.

Bibliography

Pubmed IDLast YearTitleAuthors
158825802005Id4 is required for the correct timing of neural differentiation.Bedford L et al
129698072003Id4 is deregulated by a t(6;14)(p22;q32) chromosomal translocation in a B-cell lineage acute lymphoblastic leukemia.Bellido M et al
145345432003Downregulation of ID4 by promoter hypermethylation in gastric adenocarcinoma.Chan AS et al
175105332007Frequent DNA methylation but not mutation of the ID4 gene in malignant lymphoma.Hagiwara K et al
160188212005Id4 and FABP7 are preferentially expressed in cells with astrocytic features in oligodendrogliomas and oligoastrocytomas.Liang Y et al
106112212000Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms.Massari ME et al
166824352006Inhibitors of differentiation (ID1, ID2, ID3 and ID4) genes are neuronal targets of MeCP2 that are elevated in Rett syndrome.Peddada S et al
118403232001The regulation and function of the Id proteins in lymphocyte development.Rivera R et al
165825982006Tumoral expression of BRCA1, estrogen receptor alpha and ID4 protein in patients with sporadic breast cancer.Roldán G et al
179402042008t(6;14)(p22;q32): a new recurrent IGH@ translocation involving ID4 in B-cell precursor acute lymphoblastic leukemia (BCP-ALL).Russell LJ et al
158979102005Aberrant hypermethylation of ID4 gene promoter region increases risk of lymph node metastasis in T1 breast cancer.Umetani N et al
155699772004Epigenetic inactivation of ID4 in colorectal carcinomas correlates with poor differentiation and unfavorable prognosis.Umetani N et al
158763502005Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer.Wu Q et al
157230652005Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia.Yu L et al
154699682004Id4 regulates neural progenitor proliferation and differentiation in vivo.Yun K et al
168678662006Id4 messenger RNA and estrogen receptor expression: inverse correlation in human normal breast epithelium and carcinoma.de Candia P et al

Summary

Fusion gene

IGH/ID4 IGH (14q32.33) ID4 (6p22.3) M t(6;14)(p22;q32)
Atlas Image
t(6;14)(p22;q32) G-banding and FISH - Courtesy Dorothy Hung, Luke St-Heaps and Dale Wrigh, The Cytogenetics Department of Childrens Hospital at Westmead Sydney, Australia.

Citation

Jean-Loup Huret

t(6;14)(p22;q32) IGH/ID4

Atlas Genet Cytogenet Oncol Haematol. 2008-04-01

Online version: http://atlasgeneticsoncology.org/haematological/1480/t(6;14)(p22;q32)-igh-id4

External Links