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

Written2008-04Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)


ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
Atlas_Id 1480
  t(6;14)(p22;q32) G-banding and FISH - Courtesy Dorothy Hung, Luke St-Heaps and Dale Wrigh, The Cytogenetics Department of Children's Hospital at Westmead Sydney, Australia.

Clinics and Pathology

Disease B-cell acute lymphoblastic leukaemia (B-ALL)
Phenotype / cell stem 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.
Prognosis Prognosis looks fair (see survival curve).


Cytogenetics Morphological Major karyotypic anomalies were seen in 13 of 15 cases, an i(9q) in 10/15 cases (a rather rare anomaly otherwise), +5 in 5/15, and del(13q) in 3/15. The syndrome is therefore very homogeneous, at the clinical, cytological, and cytogenetic levels.

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 NameID4 (inhibitor of DNA binding 4, dominant negative helix-loop-helix protein)
Location 6p22.3
Protein 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 NameIGH (Immunoglobulin Heavy)
Location 14q32.33

Result of the chromosomal anomaly

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


Id4 is required for the correct timing of neural differentiation.
Bedford L, Walker R, Kondo T, van Cruchten I, King ER, Sablitzky F.
Dev Biol. 2005 Apr 15;280(2):386-95.
PMID 15882580
Id4 is deregulated by a t(6;14)(p22;q32) chromosomal translocation in a B-cell lineage acute lymphoblastic leukemia.
Bellido M, Aventín A, Lasa A, Estivill C, Carnicer MJ, Pons C, Matías-Guiu X, Bordes R, Baiget M, Sierra J, Nomdedeu JF.
Haematologica. 2003 Sep;88(9):994-1001.
PMID 12969807
Downregulation of ID4 by promoter hypermethylation in gastric adenocarcinoma.
Chan AS, Tsui WY, Chen X, Chu KM, Chan TL, Chan AS, Li R, So S, Yuen ST, Leung SY.
Oncogene. 2003 Oct 9;22(44):6946-53.
PMID 14534543
Frequent DNA methylation but not mutation of the ID4 gene in malignant lymphoma.
Hagiwara K, Nagai H, Li Y, Ohashi H, Hotta T, Saito H.
J Clin Exp Hematop. 2007 Apr;47(1):15-8.
PMID 17510533
Id4 and FABP7 are preferentially expressed in cells with astrocytic features in oligodendrogliomas and oligoastrocytomas.
Liang Y, Bollen AW, Nicholas MK, Gupta N.
BMC Clin Pathol. 2005 Jul 15;5:6.
PMID 16018821
Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms.
Massari ME, Murre C.
Mol Cell Biol. 2000 Jan;20(2):429-40.
PMID 10611221
Inhibitors of differentiation (ID1, ID2, ID3 and ID4) genes are neuronal targets of MeCP2 that are elevated in Rett syndrome.
Peddada S, Yasui DH, LaSalle JM.
Hum Mol Genet. 2006 Jun 15;15(12):2003-14.
PMID 16682435
The regulation and function of the Id proteins in lymphocyte development.
Rivera R, Murre C.
Oncogene. 2001 Dec 20;20(58):8308-16.
PMID 11840323
Tumoral expression of BRCA1, estrogen receptor alpha and ID4 protein in patients with sporadic breast cancer.
Roldan G, Delgado L, Muse IM.
Cancer Biol Ther. 2006 May;5(5):505-10.
PMID 16582598
t(6;14)(p22;q32): a new recurrent IGH@ translocation involving ID4 in B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Russell LJ, Akasaka T, Majid A, Sugimoto KJ, Loraine Karran E, Nagel I, Harder L, Claviez A, Gesk S, Moorman AV, Ross F, Mazzullo H, Strefford JC, Siebert R, Dyer MJ, Harrison CJ.
Blood. 2008 Jan 1;111(1):387-91.
PMID 17940204
Aberrant hypermethylation of ID4 gene promoter region increases risk of lymph node metastasis in T1 breast cancer.
Umetani N, Mori T, Koyanagi K, Shinozaki M, Kim J, Giuliano AE, Hoon DS.
Oncogene. 2005 Jul 7;24(29):4721-7.
PMID 15897910
Epigenetic inactivation of ID4 in colorectal carcinomas correlates with poor differentiation and unfavorable prognosis.
Umetani N, Takeuchi H, Fujimoto A, Shinozaki M, Bilchik AJ, Hoon DS.
Clin Cancer Res. 2004 Nov 15;10(22):7475-83.
PMID 15569977
Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer.
Wu Q, Hoffmann MJ, Hartmann FH, Schulz WA.
Mol Cancer. 2005 May 5;4(1):16.
PMID 15876350
Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia.
Yu L, Liu C, Vandeusen J, Becknell B, Dai Z, Wu YZ, Raval A, Liu TH, Ding W, Mao C, Liu S, Smith LT, Lee S, Rassenti L, Marcucci G, Byrd J, Caligiuri MA, Plass C.
Nat Genet. 2005 Mar;37(3):265-74.
PMID 15723065
Id4 regulates neural progenitor proliferation and differentiation in vivo.
Yun K, Mantani A, Garel S, Rubenstein J, Israel MA.
Development. 2004 Nov;131(21):5441-8.
PMID 15469968
Id4 messenger RNA and estrogen receptor expression: inverse correlation in human normal breast epithelium and carcinoma.
de Candia P, Akram M, Benezra R, Brogi E.
Hum Pathol. 2006 Aug;37(8):1032-41.
PMID 16867866


This paper should be referenced as such :
Huret, JL
Atlas Genet Cytogenet Oncol Haematol. 2009;13(4):304-305.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

Genes ID4

Translocations implicated (Data extracted from papers in the Atlas)

 t(6;14)(p22;q32) IGH/ID4

External links

IGH (14q32.33) ID4 (6p22.3)

Mitelman databaset(6;14)(p22;q32)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databaseIGH::ID4 [MCList]  IGH (14q32.33) ID4 (6p22.3)
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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