| Identity |
| Other names | S171 |
| HGNC (Hugo) | NUMB |
| LocusID (NCBI) | 8650 |
| Location | 14q24.2 |
| Location_base_pair | Starts at 73741918 and ends at 73925286 bp from pter ( according to hg19-Feb_2009) [Mapping] |
| DNA/RNA |
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| Figure 1: Structure of NUMB gene. Asterisks indicate exons that undergo alternative splicing during NUMB transcript maturation. | |
| Description | The NUMB locus spans 183368 bp on the minus (-) strand of the long arm of chromosome 14 and is composed of 13 exons. |
| Transcription | As a result of three alternative splicing events the NUMB locus can generate six different transcripts of 3647 bp (isoform 1), 3503 bp (isoform 2), 3614 bp (isoform 3) and of 3470 bp (isoform 4); isoforms 5 and 6 are only partial and cover only the coding sequence and their representation* is putative. |
| Pseudogene | No known pseudogenes. |
| Protein |
![]() | |
| The modular structure of the longest human Numb isoform is shown. | |
| Description | The human Numb gene is transcribed in 6 different splicing variants (see above), due to the alternate skipping of three exons. Arrowheads indicate the boundaries of the protein sequences encoded by the three alternative exons. The PTB (Phospho-Tyrosine Binding) domain and the NumbF domain (domain found in the Numb family of proteins adjacent to the PTB domain) are indicated. The position of the DPF (responsible for binding to alpha-adaptin) and NPF motifs (responsible for binding to the EH domain of endocytic proteins) are indicated as gray and red boxes respectively. |
| Expression | From an in-silico analysis Numb RNA messenger seems broadly expressed in human tissues. However in mouse and drosophila it has been demonstrated that isoforms 1 to 4 are expressed in a tissue-specific and developmental stage-specific manner. |
| Localisation | Mostly cytosolic partially associated to the plasma membrane and vesicles; may be found also in the nucleus. |
| Function | Numb plays a multifaceted role in cellular homeostasis and is implicated in a variety of biochemical pathways connected with signaling, endocytosis, determination of polarity and ubiquitination. The pleiotropic biochemical functions of Numb lie at the heart of its involvement in diverse physiological processes, including cell fate developmental decisions, maintenance of the homeostasis of stem cell compartments, regulation of cell polarity, adhesion and migration. Loss of Numb is implicated in different types of human cancers, underscoring its complex function as a tumor suppressor in normal tissue homeostasis. The role of Numb as an intrinsic molecular determinant of cell fate during developmental programs is inextricably intertwined with the execution of asymmetric mitotic divisions, that is the mechanism through which a mother cell generates two daughter cells with different fates. The unequal distribution of Numb between two daughter cells causes a biochemical asymmetry of pathways epistatically regulated by Numb, a condition epitomized by the differential regulation of the Notch circuitry in the two daughter cells derived from the asymmetric mitotic division of the sensory organ precursor (SOP) in drosophila neurogenesis. This mechanism appears to be conserved between flies and mammals. Numb is involved at different levels in the process of endocytosis and intracellular trafficking. It interacts with the EH domain of several endocytic proteins, such as Eps15 and Eps15R, and with the major clathrin adaptor AP-2, and is subcellularly localized in endocytic/recycling organelles. Numb is also required for the internalization and recycling of transmembrane proteins, such as Sanpodo in drosophila, and different types of integrins or other transmembrane molecules in mammals.The role of Numb in the regulation of cell polarity is exerted through its interaction with core components of the evolutionary conserved Par3/Par6/aPKC (PAR) complex, and through the regulation of adherens and tight junctions. At the biochemical level, Numb is endowed with pleiotropic signaling functions. In fact, besides intersecting the Notch pathway, Numb also modulates the Hedgehog and the p53 circuitry. In general terms, the role of Numb in the regulation of specific molecular pathways is a function of a number of liaisons between Numb itself and components of the ubiquitin/proteasomal machinery. For instance, the interaction of Numb with the E3-ubiquitin ligase Itch is required for the Itch-dependent ubiquitination and ensuing proteasomal degradation of Notch. Likewise, the Numb/Itch interaction is a prerequisite for targeting Itch to the transcription factor Gli1, which ultimately affects Gli1 stability and therefore suppresses Hedgehog signaling. Furthermore, the ability of Numb to bind and inhibit the E3-ligase Hdm2 (Mdm2 in mouse) protects p53 from Hdm2-mediated ubiquitination and consequent proteasomal degradation, thus resulting in a positive regulation of the cellular levels of p53 and of its tumor suppressor activity. The downregulatory function of Numb over Hdm2 occurs in the context of a Numb/p53/Hdm2 tricomplex. Loss of this regulatory circuitry results in impaired p53-mediated cellular responses, such as apoptosis, DNA-damage and cell cycle checkpoint activation response, and is relevant to the intrinsic resistance of Numb-defective breast cancers to genotoxic agents. The networking of Numb into ubiquitin-based circuitries appears also to be at the heart of the regulation of cellular Numb levels in homeostasis. E3-ubiquitin ligases, such as Siah1 and LNX, have been implicated in targeting Numb for ubiquitin-dependent degradation. Ubiquitin-based biochemical pathways that regulate Numb levels under physiological conditions are likely relevant to cancer as well since, both in breast and in lung Numb-defective tumors, loss of Numb is due to its exaggerated ubiquitination and degradation. Considering its pleiotropic functions in many critical cellular processes, subversion of Numb has been linked to important human pathologies, and in particular to cancer. |
| Homology | Numb appears in evolution roughly with bilateral animals. Mammalian Numb homologues evolved from a common ancestral gene, possibly owing to gene duplication followed by the divergence of two gene families, Numb and Numbl. In the tree, mammalian Numb and NumbL formed two distinct clusters. A gene duplication of the ancestral Numb gene may be occurred prior to the appearance and the divergence of the major vertebrate clades, since one Numb gene is present in the chordate Ciona intestinalis, and one of the two duplicated genes evolved into NumbL via the acquisition of two Numbl unique motifs. Two of the known cellular functions to which Numb participates, endocytosis and ubiquitination, have ancient origins. Endocytosis is widely held to represent one of the distinguishing features between eukaryotes and prokaryotes. There is evidence that endocytosis is present as far back as the last eukaryotic common ancestor. In actual fact, endocytosis might be even older than this, as recent evidence demonstrates that: i) bacteria of the phyla Planctomycetes and Verrucomicrobia display intracellular membranous compartmentalization, and have membrane coat-like proteins; ii) the planctomycete Gemmata obscuriglobus exhibits endocytic-like protein uptake. Similarly, while ubiquitination is certainly one of the distinctive, and highly conserved, features of eukaryotes, its ancestry can now be traced back to bacteria, both in terms of ubiquitin-like molecules and of enzymatic molecular machinery. By the time Numb appears in phylogenesis, endocytosis and ubiquitination are already cornerstones of the eukaryotic make-up that are deeply interconnected. It is unlikely, therefore, that Numb might have evolved in direct conjunction with these processes. At the same time, the appearance of Numb roughly coincides with the appearance of the PAR complex. While polarity is perhaps as old as cellular life, a clear existence of proteins of the PAR complex can be traced back in animals only until roughly 500 million years ago, probably with the emergence of ancestors of bilateral animals (e.g., nematodes, flies and mammals). It is possible therefore that Numb evolved (or co-evolved) together with the PAR complex. Regardless, Numb might represent (and might have evolved to be) a critical connector between polarization and endocytosis. Thus, Numb might have evolved with an original role in polarity, but because of its membrane location might have subsequently acquired additional roles in the connected endocytic/ubiquitin networks: acting as a go-between between these networks and the hardware of polarity, as well as participating in them in a polarity-independent fashion. |
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| Numb in evolution. The phylogenesis of Numb in bilateral animals is shown. | |
| Mutations |
| Germinal | None found. |
| Somatic | Two mutations are reported in the COSMIC database, both of them are silent mutations: - c.1452G>T (Substitution), p.G484G (Substitution - coding silent) in one out of 447 glioma samples screened - c.354C>T (Substitution), p.A118A (Substitution - coding silent) in one out of 6 malignant melanoma samples screened. |
| Implicated in |
| Entity | Breast cancer |
| Prognosis | Loss of Numb in breast cancer correlates with poor prognosis and with clinico/pathological parameters of biological aggressiveness, such as a poorly differentiated tumor phenotype (high grade), high proliferative index (Ki67 expression), a basal-like phenotype and expression of cancer stem cell markers. |
| Oncogenesis | Numb is a tumor suppressor in the human mammary gland and its expression is frequently lost in breast cancer. Numb-defective breast tumors are addicted to loss of Numb, as witnessed by the loss of their proliferative advantage caused by re-expression of Numb. In these tumors, loss of Numb results in overactivation of oncogenic Notch signaling and impaired tumor suppression function of p53, two molecular events that are causal for transformation. Loss of Numb expression in breast cancer is due to its exaggerated ubiquitination and ensuing proteasomal degradation. |
| Entity | Lung cancer |
| Oncogenesis | The expression of Numb is frequently lost in non-small cell lung cancer (NSCLC). In NSCLC, loss of Numb results in enhanced activation of the Notch pathway, and addiction of these tumors to deregulated Notch activity. Likewise breast cancer, loss of Numb in NSCLCs is due to enhanced destruction of this protein through the proteasomal machinery. |
| Entity | Salivary gland cancer |
| Prognosis | Reduced Numb levels correlate with poor prognosis and with clinico/pathological parameters of biological aggressiveness (high grade and proliferative index) in salivary gland carcinomas. The molecular mechanism underlying loss of Numb in these tumors are not yet defined. |
| Entity | Chronic myelogenous leukemia |
| Oncogenesis | In a mouse model of chronic myelogenous leukemia (CML), Ito et al. found that reduced Numb expression is necessary for the establishment of blast crisis. A molecular mechanism different from enhanced proteasomal degradation appears to be involved in reduced Numb expression during CML progression, which is represented by the high levels of Musashi2, a repressor of Numb translation. An upregulation of Musashi2 expression was found in human CML patients during disease progression towards blast crisis, concomitant to downregulation of numb expression. |
| External links |
| Bibliography |
| numb, a gene required in determination of cell fate during sensory organ formation in Drosophila embryos. |
| Uemura T, Shepherd S, Ackerman L, Jan LY, Jan YN. |
| Cell. 1989 Jul 28;58(2):349-60. |
| PMID 2752427 |
| Asymmetric distribution of numb protein during division of the sensory organ precursor cell confers distinct fates to daughter cells. |
| Rhyu MS, Jan LY, Jan YN. |
| Cell. 1994 Feb 11;76(3):477-91. |
| PMID 8313469 |
| Asymmetric localization of numb autonomously determines sibling neuron identity in the Drosophila CNS. |
| Spana EP, Kopczynski C, Goodman CS, Doe CQ. |
| Development. 1995 Nov;121(11):3489-94. |
| PMID 8582263 |
| Control of daughter cell fates during asymmetric division: interaction of Numb and Notch. |
| Guo M, Jan LY, Jan YN. |
| Neuron. 1996 Jul;17(1):27-41. |
| PMID 8755476 |
| Numb antagonizes Notch signaling to specify sibling neuron cell fates. |
| Spana EP, Doe CQ. |
| Neuron. 1996 Jul;17(1):21-6. |
| PMID 8755475 |
| Mammalian NUMB is an evolutionarily conserved signaling adapter protein that specifies cell fate. |
| Verdi JM, Schmandt R, Bashirullah A, Jacob S, Salvino R, Craig CG, Program AE, Lipshitz HD, McGlade CJ. |
| Curr Biol. 1996 Sep 1;6(9):1134-45. |
| PMID 8805372 |
| Segregation of myogenic lineages in Drosophila requires numb. |
| Ruiz Gomez M, Bate M. |
| Development. 1997 Dec;124(23):4857-66. |
| PMID 9428422 |
| Binding specificity and in vivo targets of the EH domain, a novel protein-protein interaction module. |
| Salcini AE, Confalonieri S, Doria M, Santolini E, Tassi E, Minenkova O, Cesareni G, Pelicci PG, Di Fiore PP. |
| Genes Dev. 1997 Sep 1;11(17):2239-49. |
| PMID 9303539 |
| Differential expression of mammalian Numb, Numblike and Notch1 suggests distinct roles during mouse cortical neurogenesis. |
| Zhong W, Jiang MM, Weinmaster G, Jan LY, Jan YN. |
| Development. 1997 May;124(10):1887-97. |
| PMID 9169836 |
| The Mdm2 oncoprotein interacts with the cell fate regulator Numb. |
| Juven-Gershon T, Shifman O, Unger T, Elkeles A, Haupt Y, Oren M. |
| Mol Cell Biol. 1998 Jul;18(7):3974-82. |
| PMID 9632782 |
| Mesodermal cell fate decisions in Drosophila are under the control of the lineage genes numb, Notch, and sanpodo. |
| Park M, Yaich LE, Bodmer R. |
| Mech Dev. 1998 Jul;75(1-2):117-26. |
| PMID 9739121 |
| Characterization of four mammalian numb protein isoforms. Identification of cytoplasmic and membrane-associated variants of the phosphotyrosine binding domain. |
| Dho SE, French MB, Woods SA, McGlade CJ. |
| J Biol Chem. 1999 Nov 12;274(46):33097-104. |
| PMID 10551880 |
| Distinct human NUMB isoforms regulate differentiation vs. proliferation in the neuronal lineage. |
| Verdi JM, Bashirullah A, Goldhawk DE, Kubu CJ, Jamali M, Meakin SO, Lipshitz HD. |
| Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10472-6. |
| PMID 10468633 |
| NUMB localizes in the basal cortex of mitotic avian neuroepithelial cells and modulates neuronal differentiation by binding to NOTCH-1. |
| Wakamatsu Y, Maynard TM, Jones SU, Weston JA. |
| Neuron. 1999 May;23(1):71-81. |
| PMID 10402194 |
| Numb is an endocytic protein. |
| Santolini E, Puri C, Salcini AE, Gagliani MC, Pelicci PG, Tacchetti C, Di Fiore PP. |
| J Cell Biol. 2000 Dec 11;151(6):1345-52. |
| PMID 11121447 |
| Mouse numb is an essential gene involved in cortical neurogenesis. |
| Zhong W, Jiang MM, Schonemann MD, Meneses JJ, Pedersen RA, Jan LY, Jan YN. |
| Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6844-9. |
| PMID 10841580 |
| Siah-1 binds and regulates the function of Numb. |
| Susini L, Passer BJ, Amzallag-Elbaz N, Juven-Gershon T, Prieur S, Privat N, Tuynder M, Gendron MC, Israel A, Amson R, Oren M, Telerman A. |
| Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15067-72. |
| PMID 11752454 |
| Nucleocytoplasmic shuttling of endocytic proteins. |
| Vecchi M, Polo S, Poupon V, van de Loo JW, Benmerah A, Di Fiore PP. |
| J Cell Biol. 2001 Jun 25;153(7):1511-7. |
| PMID 11425879 |
| The endocytic protein alpha-Adaptin is required for numb-mediated asymmetric cell division in Drosophila. |
| Berdnik D, Torok T, Gonzalez-Gaitan M, Knoblich JA. |
| Dev Cell. 2002 Aug;3(2):221-31. |
| PMID 12194853 |
| LNX functions as a RING type E3 ubiquitin ligase that targets the cell fate determinant Numb for ubiquitin-dependent degradation. |
| Nie J, McGill MA, Dermer M, Dho SE, Wolting CD, McGlade CJ. |
| EMBO J. 2002 Jan 15;21(1-2):93-102. |
| PMID 11782429 |
| Asymmetric Numb distribution is critical for asymmetric cell division of mouse cerebral cortical stem cells and neuroblasts. |
| Shen Q, Zhong W, Jan YN, Temple S. |
| Development. 2002 Oct;129(20):4843-53. |
| PMID 12361975 |
| Inactivation of Numb and Numblike in embryonic dorsal forebrain impairs neurogenesis and disrupts cortical morphogenesis. |
| Li HS, Wang D, Shen Q, Schonemann MD, Gorski JA, Jones KR, Temple S, Jan LY, Jan YN. |
| Neuron. 2003 Dec 18;40(6):1105-18. |
| PMID 14687546 |
| Mammalian numb proteins promote Notch1 receptor ubiquitination and degradation of the Notch1 intracellular domain. |
| McGill MA, McGlade CJ. |
| J Biol Chem. 2003 Jun 20;278(25):23196-203. Epub 2003 Apr 7. |
| PMID 12682059 |
| Numb inhibits membrane localization of Sanpodo, a four-pass transmembrane protein, to promote asymmetric divisions in Drosophila. |
| O'Connor-Giles KM, Skeath JB. |
| Dev Cell. 2003 Aug;5(2):231-43. |
| PMID 12919675 |
| Mammalian Numb is a target protein of Mdm2, ubiquitin ligase. |
| Yogosawa S, Miyauchi Y, Honda R, Tanaka H, Yasuda H. |
| Biochem Biophys Res Commun. 2003 Mar 21;302(4):869-72. |
| PMID 12646252 |
| Distinct expression patterns of splicing isoforms of mNumb in the endocrine lineage of developing pancreas. |
| Yoshida T, Tokunaga A, Nakao K, Okano H. |
| Differentiation. 2003 Oct;71(8):486-95. |
| PMID 14641329 |
| Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis. |
| Pece S, Serresi M, Santolini E, Capra M, Hulleman E, Galimberti V, Zurrida S, Maisonneuve P, Viale G, Di Fiore PP. |
| J Cell Biol. 2004 Oct 25;167(2):215-21. Epub 2004 Oct 18. |
| PMID 15492044 |
| Localization-dependent and -independent roles of numb contribute to cell-fate specification in Drosophila. |
| Bhalerao S, Berdnik D, Torok T, Knoblich JA. |
| Curr Biol. 2005 Sep 6;15(17):1583-90. |
| PMID 16139215 |
| Targeted deletion of numb and numblike in sensory neurons reveals their essential functions in axon arborization. |
| Huang EJ, Li H, Tang AA, Wiggins AK, Neve RL, Zhong W, Jan LY, Jan YN. |
| Genes Dev. 2005 Jan 1;19(1):138-51. Epub 2004 Dec 14. |
| PMID 15598981 |
| Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination. |
| Di Marcotullio L, Ferretti E, Greco A, De Smaele E, Po A, Sico MA, Alimandi M, Giannini G, Maroder M, Screpanti I, Gulino A. |
| Nat Cell Biol. 2006 Dec;8(12):1415-23. Epub 2006 Nov 19. |
| PMID 17115028 |
| Distinct functions of human numb isoforms revealed by misexpression in the neural stem cell lineage in the Drosophila larval brain. |
| Toriya M, Tokunaga A, Sawamoto K, Nakao K, Okano H. |
| Dev Neurosci. 2006;28(1-2):142-55. |
| PMID 16508311 |
| A switch in numb isoforms is a critical step in cortical development. |
| Bani-Yaghoub M, Kubu CJ, Cowling R, Rochira J, Nikopoulos GN, Bellum S, Verdi JM. |
| Dev Dyn. 2007 Mar;236(3):696-705. |
| PMID 17253625 |
| Prognostic implications of NUMB immunoreactivity in salivary gland carcinomas. |
| Maiorano E, Favia G, Pece S, Resta L, Maisonneuve P, Di Fiore PP, Capodiferro S, Urbani U, Viale G. |
| Int J Immunopathol Pharmacol. 2007 Oct-Dec;20(4):779-89. |
| PMID 18179751 |
| Numb controls integrin endocytosis for directional cell migration with aPKC and PAR-3. |
| Nishimura T, Kaibuchi K. |
| Dev Cell. 2007 Jul;13(1):15-28. |
| PMID 17609107 |
| Polo inhibits progenitor self-renewal and regulates Numb asymmetry by phosphorylating Pon. |
| Wang H, Ouyang Y, Somers WG, Chia W, Lu B. |
| Nature. 2007 Sep 6;449(7158):96-100. |
| PMID 17805297 |
| NUMB controls p53 tumour suppressor activity. |
| Colaluca IN, Tosoni D, Nuciforo P, Senic-Matuglia F, Galimberti V, Viale G, Pece S, Di Fiore PP. |
| Nature. 2008 Jan 3;451(7174):76-80. |
| PMID 18172499 |
| Caenorhabditis elegans num-1 negatively regulates endocytic recycling. |
| Nilsson L, Conradt B, Ruaud AF, Chen CC, Hatzold J, Bessereau JL, Grant BD, Tuck S. |
| Genetics. 2008 May;179(1):375-87. |
| PMID 18493060 |
| AAK1 regulates Numb function at an early step in clathrin-mediated endocytosis. |
| Sorensen EB, Conner SD. |
| Traffic. 2008 Sep;9(10):1791-800. Epub 2008 Jul 24. |
| PMID 18657069 |
| Numb promotes an increase in skeletal muscle progenitor cells in the embryonic somite. |
| Jory A, Le Roux I, Gayraud-Morel B, Rocheteau P, Cohen-Tannoudji M, Cumano A, Tajbakhsh S. |
| Stem Cells. 2009 Nov;27(11):2769-80. |
| PMID 19785007 |
| Alterations of the Notch pathway in lung cancer. |
| Westhoff B, Colaluca IN, D'Ario G, Donzelli M, Tosoni D, Volorio S, Pelosi G, Spaggiari L, Mazzarol G, Viale G, Pece S, Di Fiore PP. |
| Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22293-8. Epub 2009 Dec 10. |
| PMID 20007775 |
| Zebrafish numb and numblike are involved in primitive erythrocyte differentiation. |
| Bresciani E, Confalonieri S, Cermenati S, Cimbro S, Foglia E, Beltrame M, Di Fiore PP, Cotelli F. |
| PLoS One. 2010 Dec 13;5(12):e14296. |
| PMID 21179188 |
| The multiple functions of Numb. |
| Gulino A, Di Marcotullio L, Screpanti I. |
| Exp Cell Res. 2010 Apr 1;316(6):900-6. Epub 2009 Nov 26. (REVIEW) |
| PMID 19944684 |
| Regulation of myeloid leukaemia by the cell-fate determinant Musashi. |
| Ito T, Kwon HY, Zimdahl B, Congdon KL, Blum J, Lento WE, Zhao C, Lagoo A, Gerrard G, Foroni L, Goldman J, Goh H, Kim SH, Kim DW, Chuah C, Oehler VG, Radich JP, Jordan CT, Reya T. |
| Nature. 2010 Aug 5;466(7307):765-8. Epub 2010 Jul 18. |
| PMID 20639863 |
| Stress-induced switch in Numb isoforms enhances Notch-dependent expression of subtype-specific transient receptor potential channel. |
| Kyriazis GA, Belal C, Madan M, Taylor DG, Wang J, Wei Z, Pattisapu JV, Chan SL. |
| J Biol Chem. 2010 Feb 26;285(9):6811-25. Epub 2009 Dec 28. |
| PMID 20038578 |
| Numb protein expression correlates with a basal-like phenotype and cancer stem cell markers in primary breast cancer. |
| Rennstam K, McMichael N, Berglund P, Honeth G, Hegardt C, Ryden L, Luts L, Bendahl PO, Hedenfalk I. |
| Breast Cancer Res Treat. 2010 Jul;122(2):315-24. Epub 2009 Oct 1. |
| PMID 19795205 |
| NUMB-ing down cancer by more than just a NOTCH. |
| Pece S, Confalonieri S, R Romano P, Di Fiore PP. |
| Biochim Biophys Acta. 2011 Jan;1815(1):26-43. Epub 2010 Oct 16. (REVIEW) |
| PMID 20940030 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 03-2011 | Stefano Confalonieri, Salvatore Pece, Pier Paolo Di Fiore |
| IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139, Milan, Italy (SC, SP, PPDF); IEO, Istituto Europeo di Oncologia, Via Ripamonti 435, 20141, Milan, Italy (SC, SP, PPDF) |
| Citation |
| This paper should be referenced as such : |
| Confalonieri S, Pece S, Di Fiore PP . NUMB (numb homolog (Drosophila)). Atlas Genet Cytogenet Oncol Haematol. March 2011 . URL : http://AtlasGeneticsOncology.org/Genes/NUMBID43702ch14q24.html |
This paper is referenced by INIST as such : |
| http://documents.irevues.inist.fr/bitstream/handle/2042/46050/03-2011-NUMBID43702ch14q24.pdf [ Bibliographic record ] |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed May 1 12:57:01 CEST 2013 |
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