identification-otx1-otx2-as-two-possible-molecular-markers-for

Identification of OTX1 and OTX2 As Two Possible Molecular Markers for Sinonasal Carcinomas and Olfactory Neuroblastomas

OTX homeobox (HB) genes are expressed during embryonic morphogenesis and during the development of olfactory epithelium in adult organisms. Mutations ...

University of Insubria

Single nucleotide polymorphisms (SNPs) are becoming the most common type of markers used in genetic analysis. In the present report a SNP has been chosen to test the applicability of Real Time PCR to discriminate and quantify SNPs alleles on DNA pools. Amplification Refractory Mutation System (ARMS) and Mismatch Amplification Mutation Assay (MAMA) has been applied. Each assay has been pre-validated testing specificity and performances (linearity, PCR efficiency, interference limit, limit of detection, limit of quantification, precision and accuracy). Both the approaches achieve a precise and accurate estimation of the allele frequencies on pooled DNA samples in the range from 5 % to 95 % and don't require standard curves or calibrators. The lowest measurement that could be significantly distinguished from the background noise has been determined around the 1 % for both the approaches, allowing to extend the range of quantifications from 1 % to 99 %. Furthermore applicability of Real Time PCR assays for general diagnostic purposes is discussed.

Different real time PCR approaches for the fine quantification of SNP's alleles in DNA pools: assays development, characterization and pre-validation.

The evaluation of residual disease, which has prognostic value in the treatment of hematological malignancies, is currently assessed by scoring a limited number of cells by karyotyping and molecular cytogenetics. Real-time polymerase chain reaction (PCR) is an easier and more sensitive technique, enables analysis of a larger number of cells, and decreases sampling error. However, real-time PCR has been applied only to target transcripts of fusion genes. Here, we considered two real-time PCR strategies to quantify a number of cells carrying a partial deletion of chromosome 7 mixed with normal disomic cells. The first strategy was based on the amplification of two sequences, one on chromosome 7 and the other on chromosome 14. In the second strategy residual disease was assessed by the ratio between the two alleles of a bi-allelic marker, mapped on chromosome 7, measured with allele-specific assays. Precision and accuracy of the two approaches were tested by reference samples with nominal values of residual disease ranging from 2 to 95%. As expected the second strategy resulted in more precise and accurate monitoring within the range from 5 to 95%. Furthermore, this method may be applied to assess the number of dysplastic or neoplastic clones carrying any unbalanced chromosome changes.

Establishment and study of different real-time polymerase chain reaction assays for the quantification of cells with deletions of chromosome 7.

&#x4E73;&#x817A;&#x72EC;&#x7279;&#x7684;&#x673A;&#x6784;&#x7684;&#x4E3B;&#x8981;&#x5F62;&#x5F0F;&#xFF0C;&#x9752;&#x6625;&#x671F;&#x662F;&#x4E00;&#x4E2A;&#x7406;&#x60F3;&#x7684;&#x6A21;&#x578B;&#xFF0C;&#x4EE5;&#x7814;&#x7A76;&#x5728;&#x53D1;&#x5C55;&#x548C;&#x80BF;&#x7624;&#x53D1;&#x751F; (HB) &#x540C;&#x6E90;&#x76D2;&#x57FA;&#x56E0;&#x7684;&#x529F;&#x80FD;&#x3002;HB &#x57FA;&#x56E0;&#x7EC4;&#x6210;&#x4E00;&#x4E2A;&#x5927;&#x5BB6;&#x5EAD;&#x7684;&#x53D1;&#x5C55;&#x5177;&#x6709;&#x5173;&#x952E;&#x4F5C;&#x7528;&#xFF0C;&#x7EC6;&#x80DE;&#x751F;&#x957F;&#x548C;&#x5206;&#x5316;&#x7684;&#x76D1;&#x7BA1;&#x3002;&#x5728;&#x6B63;&#x5E38;&#x7684;&#x4E73;&#x817A;&#x7EC4;&#x7EC7;&#xFF0C;&#x540C;&#x6E90;&#x76D2;&#x57FA;&#x56E0;&#x53C2;&#x4E0E;&#x5BFC;&#x7BA1;&#x5F62;&#x6210;&#x3001; &#x4E0A;&#x76AE;&#x5206;&#x652F;&#x548C; lobulo &#x80BA;&#x6CE1;&#x53D1;&#x5C55;&#x7684;&#x89C4;&#x7BA1;&#x4E0A;&#x76AE;&#x7EC6;&#x80DE;&#x589E;&#x6B96;&#x548C;&#x5206;&#x5316;&#x3002;HB &#x57FA;&#x56E0;&#x63A7;&#x5236;&#x57FA;&#x8D28;&#x7EC6;&#x80DE;&#x548C;&#x4E0A;&#x76AE;&#x7EC6;&#x80DE;&#x4E2D;&#x7684;&#x7A7A;&#x95F4;&#x548C;&#x65F6;&#x95F4;&#x7684;&#x65B9;&#x5F0F;&#x3002;&#x4ED6;&#x4EEC;&#x534F;&#x8C03;&#x53D7;&#x6FC0;&#x7D20;&#x548C;&#x7EC6;&#x80DE;&#x5916;&#x57FA;&#x8D28;&#xFF0C;&#x8FD9;&#x8868;&#x660E;&#x8BB8;&#x591A;&#x4FE1;&#x53F7;&#x901A;&#x8DEF;&#x53C2;&#x4E0E;&#x4E86;&#x540C;&#x6E90;&#x76D2;&#x57FA;&#x56E0;&#x529F;&#x80FD;&#x3002;&#x540C;&#x6E90;&#x76D2;&#x57FA;&#x56E0; misexpressed &#x5728;&#x52A8;&#x7269;&#x6A21;&#x578B;&#x4E2D;&#xFF0C;&#x5F53;&#x5728;&#x4E73;&#x817A;&#x53D1;&#x80B2;&#x4E2D;&#x663E;&#x793A;&#x4E0D;&#x540C;&#x7684;&#x7F3A;&#x9677;&#x3002;&#x5F02;&#x5E38;&#x8868;&#x8FBE;&#x7684;&#x540C;&#x6E90;&#x76D2;&#x57FA;&#x56E0;&#xFF0C;&#x5916;&#x57DF;&#x6216;&#x7F16;&#x7801;&#xFF0C;&#x627E;&#x5230;&#x539F;&#x53D1;&#x764C;&#x548C;&#x4E73;&#x817A;&#x764C;&#x3002;Otx1 &#x8840;&#x7EA2;&#x86CB;&#x767D;&#x57FA;&#x56E0;&#x662F;&#x76D1;&#x7BA1;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x53D1;&#x80B2;&#x80DA;&#x80CE;&#x53D1;&#x751F;&#x8FC7;&#x7A0B;&#x4E2D;&#x7684;&#x4E00;&#x4E2A;&#x7ECF;&#x5178;&#x3002;Otx1 &#x5728;&#x5782;&#x4F53;&#x524D;&#x7684;&#x8F6C;&#x5F55;&#x5E76;&#x5728;&#x6FC0;&#x6D3B;&#x7684;&#x5782;&#x4F53;&#x6FC0;&#x7D20;&#x3001; &#x8F6C;&#x5F55;&#x548C;&#x9020;&#x8840;&#x529F;&#x80FD;&#x3001; &#x589E;&#x5F3A;&#x7684;&#x591A;&#x80FD;&#x5E72;&#x7EC6;&#x80DE;&#x548C;&#x7EA2;&#x7CFB;&#x5206;&#x5316;&#x4E2D;&#x7684;&#x4F5C;&#x7528;&#x3002;Otx1 &#x4ECD;&#x5728;&#x7EA2;&#x7EC6;&#x80DE;&#x548C; megacaryocytic &#x6CBF;&#x88AD;&#x7684;&#x6210;&#x719F;&#x7EC6;&#x80DE;&#x4E2D;&#x68C0;&#x6D4B;&#x5230;&#x3002;&#x5468;&#x671F;&#x6027;&#x53D1;&#x5C55;&#x8FC7;&#x7A0B;&#x7684;&#x4E73;&#x817A;&#x7EC4;&#x7EC7;&#x4E2D;&#xFF0C;Otx1 &#x57FA;&#x56E0;&#x6297;&#x539F;&#x5728;&#x54FA;&#x4E73;&#x671F;&#xFF0C;&#x786E;&#x8BA4;&#x6B64;&#x8F6C;&#x5F55;&#x56E0;&#x5B50;&#x5728;&#x7EC6;&#x80DE;&#x5206;&#x5316;&#x4E2D;&#x7684;&#x4F5C;&#x7528;&#x3002;&#x6700;&#x8FD1;&#x7684;&#x7814;&#x7A76;&#x62A5;&#x544A; Otx1 &#x6297;&#x539F;&#x5728;&#x4E73;&#x817A;&#x764C;&#x3002;&#x5728;&#x80DA;&#x80CE;&#x53D1;&#x751F;&#xFF0C;&#x671F;&#x95F4;&#x8868;&#x793A;&#xFF0C;Otx1&#xFF0C;&#x5B83;&#x764C;&#x53D8;&#xFF0C;&#x8FD9;&#x610F;&#x5473;&#x7740;&#x5176;&#x53EF;&#x80FD;&#x529F;&#x80FD;&#x7684;&#x80BF;&#x7624;&#x7EC6;&#x80DE;&#x5206;&#x5316;&#x8FC7;&#x7A0B;&#x4E2D;&#x518D;&#x6B21;&#x8868;&#x793A;&#x3002;

&#x4E73;&#x817A;&#x7EC4;&#x7EC7;&#x548C; Otx1 &#x7684;&#x540C;&#x6E90;&#x76D2;&#x57FA;&#x56E0;&#x3002;

The mammary gland, the unique organ that primarily form at puberty, is an ideal model to study the functions of homeobox (HB) genes in both development and tumorigenesis. HB genes comprise a large family of developmental regulators that have a critical role in cell growth and differentiation. In the normal mammary gland, homeobox genes are involved in ductal formation, epithelial branching, and lobulo-alveolar development by regulating epithelial proliferation and differentiation. The HB genes are controlled in a spatial and temporal manner in both stromal and epithelial cells. They are coordinately regulated by hormones and extracellular matrix, suggesting that many signaling pathways are involved in homeobox gene functions. When homeobox genes are misexpressed in animal models, different defects are displayed in mammary gland development. Aberrant expression of homeobox genes, overexpressed or downregulated, is found in primary carcinomas and in breast cancer. The Otx1 HB gene is a classic regulatory of nervous system development during embryogenesis. Postnatally Otx1 is transcribed in the anterior pituitary gland, where activates transcription of the pituitary hormones, and plays a role in hematopoiesis, enhancing pluripotent cells, and erythroid differentiation. Otx1 can still be detected in mature cells of the erythroid and megacaryocytic lineage. During cyclical development of mammary gland, the Otx1 gene is overexpressed in lactation, confirming a role of this transcription factor in cell differentiation. Recent studies report that Otx1 is overexpressed in breast cancer. Otx1 is expressed during embryogenesis, and it is expressed again during carcinogenesis, implying its possible function in differentiation of neoplastic cells.

The mammary gland and the homeobox gene Otx1.

La glande mammaire, l&#39;unique organe qui forment principalement &agrave; la pubert&eacute;, est un mod&egrave;le id&eacute;al pour &eacute;tudier les fonctions des g&egrave;nes homeobox (HB) dans le d&eacute;veloppement et la tumorigen&egrave;se. G&egrave;nes HB forment une grande famille de r&eacute;gulateurs du d&eacute;veloppement qui ont un r&ocirc;le essentiel dans la croissance cellulaire et la diff&eacute;renciation. Dans la glande mammaire normale, homeobox g&egrave;nes sont impliqu&eacute;s dans la formation de ductal, ramification &eacute;pith&eacute;liales et d&eacute;veloppement lobulo-alv&eacute;olaire en r&eacute;gulant la diff&eacute;renciation et la prolif&eacute;ration &eacute;pith&eacute;liale. Les g&egrave;nes de HB sont contr&ocirc;l&eacute;s de fa&ccedil;on spatiale et temporelle en tant les cellules &eacute;pith&eacute;liales du stroma. Coordonner, ils sont r&eacute;glement&eacute;s par les hormones et la matrice extracellulaire, ce qui sugg&egrave;re que les nombreuses voies de signalisation sont impliqu&eacute;s dans les fonctions du g&egrave;ne hom&eacute;otique. Lorsque homeobox g&egrave;nes sont misexpressed dans des mod&egrave;les animaux, diff&eacute;rents d&eacute;fauts sont affich&eacute;es dans le d&eacute;veloppement de la glande mammaire. Expression aberrante de homeobox g&egrave;nes surexprim&eacute;s ou r&eacute;prim&eacute;s, se trouve dans les carcinomes primaires et dans le cancer du sein. Le g&egrave;ne Otx1 HB est un classique r&eacute;glementaire du d&eacute;veloppement du syst&egrave;me nerveux au cours de l&#39;embryogen&egrave;se. Apr&egrave;s la naissance Otx1 est transcrit dans l&#39;hypophyse ant&eacute;rieure, o&ugrave; active la transcription des hormones hypophysaires, et joue un r&ocirc;le dans l&#39;h&eacute;matopo&iuml;&egrave;se, renforcement des cellules pluripotentes et la diff&eacute;renciation &eacute;rythro&iuml;de. Otx1 peut encore &ecirc;tre d&eacute;tect&eacute; dans les cellules matures de la lign&eacute;e &eacute;rythro&iuml;de et megacaryocytic. Au cours du d&eacute;veloppement cyclique de la glande mammaire, le g&egrave;ne Otx1 est surexprim&eacute; dans la lactation, confirmant le r&ocirc;le de ce facteur de transcription dans la diff&eacute;renciation cellulaire. Des &eacute;tudes r&eacute;centes rapportent que Otx1 est surexprim&eacute;e dans le cancer du sein. Otx1 est exprim&eacute;e au cours de l&#39;embryogen&egrave;se, et il s&#39;exprime encore une fois au cours de la canc&eacute;rogen&egrave;se, ce qui implique son r&ocirc;le possible dans la diff&eacute;renciation des cellules n&eacute;oplasiques.

La glande mammaire et le g&egrave;ne hom&eacute;otique Otx1.

Der Brustdr&uuml;se, die einzigartige Orgel, die vor allem in der Pubert&auml;t, zu bilden ist ein ideales Modell, um die Funktionen der (HB) Hox-Gene sowohl die Entwicklung als auch die Tumorentstehung zu studieren. HB-Gene umfassen eine gro&szlig;e Familie von Entwicklungsst&ouml;rungen Regulatoren, die eine entscheidende Rolle im Zellwachstum und Differenzierung. In der normalen Brustdr&uuml;se sind Hox-Gene in duktale Formation, epitheliale verzweigen und Lobulo-alveol&auml;re Entwicklung beteiligt, durch die Regulierung epitheliale Proliferation und Differenzierung. Die HB-Gene werden in einer r&auml;umlichen und zeitlichen Weise in sowohl stromal und epitheliale Zellen gesteuert. Sie sind coordinately geregelt durch Hormone und extrazellul&auml;re Matrix, was darauf hindeutet, dass viele Signalwege in Homeobox Genfunktionen beteiligt sind. Wenn Hox-Gene in Tiermodellen misexpressed sind, werden verschiedene M&auml;ngel in der Brustdr&uuml;se Entwicklung angezeigt. Aberrante Expression von Hox-Gene, Pleuramesotheliom oder Downregulated, befinden sich in prim&auml;re Karzinome sowie bei Brustkrebs. Das Otx1 HB-gen ist ein Klassiker, der Regulierung des Nervensystems Entwicklung w&auml;hrend der Embryogenese. Postnatal ist Otx1 in den vorderen Hypophyse, transkribiert wo Transkription der Hypophyse Hormone aktiviert, und spielt eine Rolle bei der Blutbildung, Verbesserung pluripotenten Zellen und Erythroid Differenzierung. Otx1 k&ouml;nnen noch im Reifen Zellen der Erythroid und Megacaryocytic Abstammung nachgewiesen werden. W&auml;hrend der zyklischen Entwicklung der Brustdr&uuml;se ist das Otx1-gen in der Stillzeit, best&auml;tigt eine Rolle dieser Transkriptionsfaktor in Zelldifferenzierung Pleuramesotheliom. Neuere Studien berichten, dass Otx1 bei Brustkrebs Pleuramesotheliom ist. Otx1 wird w&auml;hrend der Embryogenese exprimiert, und wieder w&auml;hrend der Karzinogenese, was seine m&ouml;gliche Funktion in der Differenzierung der neoplastischen Zellen ausgedr&uuml;ckt wird.

Der Brustdr&uuml;se und der Hom&ouml;obox-gen Otx1.

La ghiandola mammaria, l&#39;unico organo che formano principalmente durante la pubert&agrave;, &egrave; un modello ideale per studiare le funzioni dei geni homeobox (HB) lo sviluppo e la tumorigenesi. Geni HB costituiscono una grande famiglia di regolatori dello sviluppo che hanno un ruolo critico nella crescita cellulare e la differenziazione. Nella ghiandola mammaria normale, homeobox geni sono coinvolti nella formazione duttale, ramificazione epiteliale e sviluppo lobulo-alveolare regolando la differenziazione e la proliferazione epiteliale. I geni di HB sono controllati in modo spaziale e temporale in cellule stromali ed epiteliali. Coordinately sono regolati da ormoni e matrice extracellulare, suggerendo che nelle funzioni del gene homeobox sono coinvolte molte vie di segnalazione. Quando i geni dell&#39;homeobox sono misexpressed in modelli animali, vengono visualizzati diversi difetti nello sviluppo della ghiandola mammaria. Aberrante espressione di geni homeobox, overexpressed o downregolata, &egrave; trovato in carcinomi primari e nel cancro al seno. Il gene Otx1 HB &egrave; un classico regolamentazione dello sviluppo del sistema nervoso durante l&#39;embriogenesi. Dopo la nascita &egrave; trascritto Otx1 nella ghiandola pituitaria anteriore, dove attiva la trascrizione degli ormoni ipofisari, e svolge un ruolo nella differenziazione eritroide ematopoiesi e migliorare le cellule pluripotenti. Otx1 pu&ograve; ancora essere rilevato in cellule mature del lignaggio eritroidi e megacaryocytic. Durante lo sviluppo ciclico della ghiandola mammaria, il gene Otx1 &egrave; overexpressed in lattazione, confermando un ruolo di questo fattore di trascrizione nel differenziamento cellulare. Studi recenti riportano che Otx1 &egrave; overexpressed nel cancro al seno. Otx1 &egrave; espresso durante l&#39;embriogenesi e si esprime ancora una volta durante la carcinogenesi, implicando la sua possibile funzione di differenziazione delle cellule neoplastiche.

La ghiandola mammaria e il homeobox gene Otx1.

&#x4E3B;&#x306B;&#x601D;&#x6625;&#x671F;&#x306B;&#x306F;&#x3001;&#x30D5;&#x30A9;&#x30FC;&#x30E0;&#x56FA;&#x6709;&#x306E;&#x81D3;&#x5668;&#x306E;&#x4E73;&#x817A;&#x306E;&#x958B;&#x767A;&#x3068;&#x816B;&#x760D;&#x767A;&#x751F;&#x306B;&#x304A;&#x3051;&#x308B;&#x30DB;&#x30E1;&#x30AA; &#x30DC;&#x30C3;&#x30AF;&#x30B9; (HB) &#x907A;&#x4F1D;&#x5B50;&#x6A5F;&#x80FD;&#x7814;&#x7A76;&#x306B;&#x7406;&#x60F3;&#x7684;&#x306A;&#x30E2;&#x30C7;&#x30EB;&#x3067;&#x3059;&#x3002;HB &#x907A;&#x4F1D;&#x5B50;&#x306F;&#x7D30;&#x80DE;&#x5897;&#x6B96;&#x3068;&#x5206;&#x5316;&#x306B;&#x91CD;&#x8981;&#x306A;&#x5F79;&#x5272;&#x304C;&#x3042;&#x308B;&#x767A;&#x9054;&#x306E;&#x30EC;&#x30AE;&#x30E5;&#x30EC;&#x30FC;&#x30BF;&#x306E;&#x5927;&#x5BB6;&#x65CF;&#x3092;&#x69CB;&#x6210;&#x3057;&#x307E;&#x3059;&#x3002;&#x6B63;&#x5E38;&#x4E73;&#x817A;&#x306E;&#x30DB;&#x30E1;&#x30AA; &#x30DC;&#x30C3;&#x30AF;&#x30B9;&#x907A;&#x4F1D;&#x5B50;&#x4E73;&#x7BA1;&#x5F62;&#x6210;, &#x4E0A;&#x76AE;&#x5206;&#x5C90;&#x3068; lobulo &#x6B6F;&#x69FD;&#x958B;&#x767A;&#x4E0A;&#x76AE;&#x306E;&#x5897;&#x6B96;&#x3068;&#x5206;&#x5316;&#x3092;&#x8ABF;&#x7BC0;&#x3059;&#x308B;&#x3053;&#x3068;&#x306B;&#x3088;&#x3063;&#x3066;&#x304B;&#x304B;&#x308F;&#x3063;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;HB &#x907A;&#x4F1D;&#x5B50;&#x9593;&#x8CEA;&#x7D30;&#x80DE;&#x306A;&#x3089;&#x3073;&#x306B;&#x4E0A;&#x76AE;&#x7D30;&#x80DE;&#x3067;&#x306E;&#x6642;&#x7A7A;&#x7684;&#x5236;&#x5FA1;&#x3055;&#x308C;&#x307E;&#x3059;&#x3002;&#x30DB;&#x30EB;&#x30E2;&#x30F3;&#x3068;&#x7D30;&#x80DE;&#x5916;&#x30DE;&#x30C8;&#x30EA;&#x30C3;&#x30AF;&#x30B9;&#x306B;&#x3088;&#x3063;&#x3066;&#x591A;&#x304F;&#x306E;&#x30B7;&#x30B0;&#x30CA;&#x30EB;&#x4F1D;&#x9054;&#x7D4C;&#x8DEF;&#x30DB;&#x30E1;&#x30AA; &#x30DC;&#x30C3;&#x30AF;&#x30B9;&#x907A;&#x4F1D;&#x5B50;&#x306E;&#x6A5F;&#x80FD;&#x306B;&#x95A2;&#x4E0E;&#x3057;&#x3066;&#x3044;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x5506;&#x5F7C;&#x3089;&#x30EA;&#x30BA;&#x30DF;&#x30AB;&#x30EB;&#x898F;&#x5236;&#x3055;&#x308C;&#x307E;&#x3059;&#x3002;&#x30DB;&#x30E1;&#x30AA; &#x30DC;&#x30C3;&#x30AF;&#x30B9;&#x907A;&#x4F1D;&#x5B50;&#x304C;&#x52D5;&#x7269;&#x30E2;&#x30C7;&#x30EB;&#x3067; misexpressed &#x3044;&#x308B;&#x3068;&#x304D;&#x306B;&#x3001;&#x7570;&#x306A;&#x308B;&#x6B20;&#x9665;&#x4E73;&#x817A;&#x306E;&#x958B;&#x767A;&#x3067;&#x8868;&#x793A;&#x3055;&#x308C;&#x307E;&#x3059;&#x3002;&#x7570;&#x5E38;&#x767A;&#x73FE;&#x306E;&#x30DB;&#x30E1;&#x30AA; &#x30DC;&#x30C3;&#x30AF;&#x30B9;&#x907A;&#x4F1D;&#x5B50;&#x306E;&#x904E;&#x5270;&#x767A;&#x73FE;&#x307E;&#x305F;&#x306F; downregulated&#x3001;&#x30D7;&#x30E9;&#x30A4;&#x30DE;&#x30EA;&#x764C;&#x3068;&#x4E73;&#x764C;&#x3092;&#x767A;&#x898B;&#x3057;&#x307E;&#x3059;&#x3002;Otx1 HB &#x907A;&#x4F1D;&#x5B50;&#x30AF;&#x30E9;&#x30B7;&#x30C3;&#x30AF;&#x306A;&#x80DA;&#x5F62;&#x6210;&#x904E;&#x7A0B;&#x306B;&#x304A;&#x3051;&#x308B;&#x795E;&#x7D4C;&#x7CFB;&#x958B;&#x767A;&#x306E;&#x898F;&#x5236;&#x3067;&#x3059;&#x3002;&#x5C3F;&#x8DEF;&#x30C9;&#x30EC;&#x30CA;&#x30FC;&#x30B8; Otx1 &#x8133;&#x4E0B;&#x5782;&#x4F53;&#x524D;&#x8449;&#x3001;&#x8EE2;&#x5199;&#x3055;&#x308C;&#x308B;&#x5834;&#x6240;&#x3001;&#x4E0B;&#x5782;&#x4F53;&#x30DB;&#x30EB;&#x30E2;&#x30F3;&#x306E;&#x8EE2;&#x5199;&#x3092;&#x6D3B;&#x6027;&#x5316;&#x3057;&#x3001;&#x9020;&#x8840;&#x3001;&#x5F37;&#x5316;&#x591A;&#x80FD;&#x6027;&#x7D30;&#x80DE;&#x3001;&#x8D64;&#x8840;&#x7403;&#x5206;&#x5316;&#x306B;&#x304A;&#x3051;&#x308B;&#x5F79;&#x5272;&#x3092;&#x679C;&#x305F;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;Otx1 &#x306F;&#x3001;&#x307E;&#x3060;&#x8D64;&#x82BD;&#x7403;&#x304A;&#x3088;&#x3073; megacaryocytic &#x306E;&#x7CFB;&#x7D71;&#x306E;&#x6210;&#x719F;&#x7D30;&#x80DE;&#x3067;&#x691C;&#x51FA;&#x3067;&#x304D;&#x307E;&#x3059;&#x3002;&#x4E73;&#x817A;&#x306E;&#x5FAA;&#x74B0;&#x306E;&#x958B;&#x767A;&#x4E2D;&#x306F;&#x3001;Otx1 &#x907A;&#x4F1D;&#x5B50;&#x3092;&#x904E;&#x5270;&#x767A;&#x73FE;&#x6388;&#x4E73;&#x671F;&#x3001;&#x3053;&#x306E;&#x7D30;&#x80DE;&#x306E;&#x5206;&#x5316;&#x306B;&#x304A;&#x3051;&#x308B;&#x8EE2;&#x5199;&#x56E0;&#x5B50;&#x306E;&#x5F79;&#x5272;&#x3092;&#x78BA;&#x8A8D;&#x3057;&#x307E;&#x3059;&#x3002;&#x6700;&#x8FD1;&#x306E;&#x7814;&#x7A76;&#x306F;&#x3001;Otx1 &#x304C;&#x4E73;&#x764C;&#x3067;&#x904E;&#x5270;&#x306B;&#x767A;&#x73FE;&#x5831;&#x544A;&#x3057;&#x307E;&#x3059;&#x3002;Otx1 &#x80DA;&#x767A;&#x751F;&#x4E2D;&#x306B;&#x8868;&#x73FE;&#x3055;&#x308C;&#x3001;&#x518D;&#x3073;&#x767A;&#x304C;&#x3093;, &#x305D;&#x306E;&#x816B;&#x760D;&#x7D30;&#x80DE;&#x306E;&#x5206;&#x5316;&#x306B;&#x304A;&#x3051;&#x308B;&#x53EF;&#x80FD;&#x306A;&#x6A5F;&#x80FD;&#x3092;&#x610F;&#x5473;&#x3057;&#x3066;&#x4E2D;&#x3092;&#x8868;&#x660E;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;

&#x4E73;&#x817A;&#x3068;&#x30DB;&#x30E1;&#x30AA; &#x30DC;&#x30C3;&#x30AF;&#x30B9;&#x907A;&#x4F1D;&#x5B50; Otx1&#x3002;

&#xC720; &#xBC29; &#xC120;, &#xC8FC;&#xB85C; &#xC0AC;&#xCD98;&#xAE30;&#xC5D0; &#xD615;&#xC131; &#xD558;&#xB294; &#xB3C5;&#xD2B9;&#xD55C; &#xAE30;&#xAD00; &#xAC1C;&#xBC1C; &#xBC0F; tumorigenesis (HB) homeobox &#xC720;&#xC804;&#xC790;&#xC758; &#xAE30;&#xB2A5; &#xC5F0;&#xAD6C;&#xC5D0; &#xC774;&#xC0C1;&#xC801;&#xC778; &#xBAA8;&#xB378;&#xC785;&#xB2C8;&#xB2E4;. HB &#xC720;&#xC804;&#xC790; &#xC138;&#xD3EC; &#xC131;&#xC7A5;&#xACFC; &#xBD84;&#xD654;&#xC5D0; &#xC911;&#xC694; &#xD55C; &#xC5ED;&#xD560;&#xC744;&#xAC00;&#xC9C0;&#xACE0; &#xBC1C;&#xB2EC; &#xB808; &#xADE4; &#xB808;&#xC774; &#xD130;&#xC758; &#xD070; &#xAC00;&#xC871;&#xC73C;&#xB85C; &#xAD6C;&#xC131; &#xB429;&#xB2C8;&#xB2E4;. &#xC77C;&#xBC18; &#xC720;&#xC120; &#xC120; homeobox &#xC720;&#xC804;&#xC790;&#xB294; &#xC0C1;&#xD53C; &#xC99D;&#xC2DD;&#xACFC; &#xBD84;&#xD654;&#xB97C; &#xC870;&#xC808; &#xD558; &#xC5EC; ductal &#xD615;&#xC131;, &#xC0C1;&#xD53C; &#xBD84;&#xAE30; &#xBC0F; lobulo &#xCE58;&#xACBD; &#xAC1C;&#xBC1C;&#xC5D0;&#xC11C; &#xD3EC;&#xD568; &#xB41C;&#xB2E4;. HB &#xC720;&#xC804;&#xC790;&#xB294; &#xAE30;&#xC9C8;&#xACFC; &#xC0C1;&#xD53C; &#xC138;&#xD3EC;&#xC5D0;&#xC11C; &#xACF5;&#xAC04; &#xBC0F; &#xC2DC;&#xAC04; &#xBC29;&#xC2DD;&#xC73C;&#xB85C; &#xC81C;&#xC5B4; &#xB429;&#xB2C8;&#xB2E4;. &#xADF8;&#xB4E4;&#xC740; coordinately &#xC81C;&#xC548; &#xD558;&#xB294; &#xB9CE;&#xC740; &#xC2E0;&#xD638; &#xACBD;&#xB85C; homeobox &#xC720;&#xC804;&#xC790; &#xAE30;&#xB2A5;&#xC5D0; &#xAD00;&#xB828; &#xB41C; &#xD638;&#xB974;&#xBAAC;&#xACFC; &#xC138;&#xD3EC; &#xC678; &#xB9E4;&#xD2B8;&#xB9AD;&#xC2A4;&#xC5D0; &#xC758;&#xD574; &#xD1B5;&#xC81C; &#xB41C;&#xB2E4;. Homeobox &#xC720;&#xC804;&#xC790;&#xB294; &#xB3D9;&#xBB3C; &#xBAA8;&#xB378;&#xC5D0;&#xC11C; misexpressed&#xB294;, &#xC720;&#xC120; &#xBC1C;&#xB2EC;&#xC5D0; &#xB2E4;&#xB978; &#xACB0;&#xD568;&#xC774; &#xD45C;&#xC2DC; &#xB429;&#xB2C8;&#xB2E4;. Overexpressed homeobox &#xC720;&#xC804;&#xC790; &#xB610;&#xB294; downregulated, &#xD0C8; &#xC120; &#xC2DD; &#xC8FC; carcinomas &#xBC0F; &#xC720;&#xBC29;&#xC554; &#xBC1C;&#xACAC; &#xB41C;&#xB2E4;. Otx1 HB &#xC720;&#xC804;&#xC790; embryogenesis &#xC911; &#xC2E0; &#xC2DC;&#xC2A4;&#xD15C; &#xAC1C;&#xBC1C;&#xC758; &#xADDC;&#xC81C; &#xACE0;&#xC804; &#xC774;&#xB2E4;. Postnatally Otx1 &#xC55E;&#xCABD;&#xC5D0; &#xB1CC; &#xD558; &#xC218; &#xCCB4;&#xC5D0;&#xC11C; &#xBCC0;&#xD558;&#xAC8C; &#xB418; &#xC788;&#xB294; &#xB1CC; &#xD558; &#xC218; &#xCCB4; &#xD638;&#xB974;&#xBAAC;&#xC758; &#xC804;&#xC0AC;&#xB97C; &#xD65C;&#xC131;&#xD654; &#xD558; &#xACE0; &#xC870;, &#xAC15;&#xD654; pluripotent &#xC140; &#xBC0F; erythroid &#xCC28;&#xBCC4;&#xD654;&#xC5D0; &#xC5ED;&#xD560;&#xC744; &#xD55C;&#xB2E4;. Otx1 erythroid &#xBC0F; megacaryocytic &#xD608;&#xD1B5;&#xC758; &#xC131;&#xC219;&#xD55C; &#xC138;&#xD3EC;&#xC5D0;&#xC11C; &#xC5EC;&#xC804;&#xD788; &#xAC10;&#xC9C0;&#xD560; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC720;&#xC120;&#xC758; &#xC21C;&#xD658;&#xC801;&#xC778; &#xAC1C;&#xBC1C; &#xD558;&#xB294; &#xB3D9;&#xC548; Otx1 &#xC720;&#xC804;&#xC790;&#xB294; &#xC138;&#xD3EC; &#xBD84;&#xD654;&#xC5D0;&#xC774; &#xB179;&#xC74C; &#xBC29;&#xC1A1; &#xC694;&#xC778;&#xC758; &#xC5ED;&#xD560;&#xC744; &#xD655;&#xC778; &#xD558;&#xB294; &#xC218; &#xC720;&#xC5D0; overexpressed&#xC785;&#xB2C8;&#xB2E4;. &#xCD5C;&#xADFC; &#xC5F0;&#xAD6C; &#xBCF4;&#xACE0; Otx1 &#xC720;&#xBC29;&#xC554;&#xC5D0; overexpressed&#xC785;&#xB2C8;&#xB2E4;. Otx1&#xC740; embryogenesis, &#xB3D9;&#xC548; &#xD45C;&#xD604; &#xB418; &#xACE0; &#xBC1C;&#xC554;, &#xC885;&#xC591; &#xC57D; &#xC138;&#xD3EC;&#xC758; &#xBD84;&#xD654;&#xC5D0; &#xAC00;&#xB2A5;&#xD55C; &#xAE30;&#xB2A5;&#xC744; &#xC554;&#xC2DC; &#xD558;&#xB294; &#xB3D9;&#xC548; &#xB2E4;&#xC2DC; &#xD45C;&#xC2DC; &#xB429;&#xB2C8;&#xB2E4;.

&#xC720;&#xC120; &#xBC0F; homeobox &#xC720;&#xC804;&#xC790; otx1&#xC785;&#xB2C8;&#xB2E4;.

La gl&aacute;ndula mamaria, el &uacute;nico &oacute;rgano que forman sobre todo en la pubertad, es un modelo ideal para estudiar las funciones de los genes homeobox (HB) en desarrollo y de la tumorig&eacute;nesis. Genes HB forman una gran familia de reguladores del desarrollo que tienen un papel fundamental en el crecimiento celular y diferenciaci&oacute;n. En la gl&aacute;ndula mamaria normal, homeobox genes est&aacute;n involucrados en formaci&oacute;n ductal, ramificaci&oacute;n epitelial y desarrollo lobulo-alveolar mediante la regulaci&oacute;n de la diferenciaci&oacute;n y proliferaci&oacute;n epitelial. Los genes de HB son controlados de manera espacial y temporal en las c&eacute;lulas epiteliales y estromales. Coordinadamente se regulan por las hormonas y la matriz extracelular, lo que sugiere que muchas v&iacute;as de se&ntilde;alizaci&oacute;n est&aacute;n implicadas en las funciones de genes homeobox. Cuando genes homeobox se misexpressed en modelos animales, aparecen diferentes defectos en el desarrollo de la gl&aacute;ndula mamaria. Expresi&oacute;n aberrante de genes homeobox, sobreexpresa o reguladas, se encuentra en carcinomas primarios y en c&aacute;ncer de mama. El gen Otx1 HB es un cl&aacute;sico de regulaci&oacute;n del desarrollo del sistema nervioso durante la embriog&eacute;nesis. Postnatal Otx1 se transcribe en la gl&aacute;ndula pituitaria anterior, donde activa la transcripci&oacute;n de las hormonas hipofisarias y desempe&ntilde;a un papel en la diferenciaci&oacute;n eritroide, hematopoyesis y c&eacute;lulas aumento pluripotentes. Otx1 todav&iacute;a pueden detectarse en las c&eacute;lulas maduras del linaje eritroide y megacaryocytic. Durante el desarrollo c&iacute;clico de la gl&aacute;ndula mamaria, el gen Otx1 se sobreexpresa en lactancia, confirmando un papel de este factor de transcripci&oacute;n en la diferenciaci&oacute;n celular. Estudios recientes informan que Otx1 se sobreexpresa en c&aacute;ncer de mama. Otx1 se expresa durante la embriog&eacute;nesis, y se expresa una vez m&aacute;s durante la carcinog&eacute;nesis, lo que implica su posible funci&oacute;n en la diferenciaci&oacute;n de las c&eacute;lulas neopl&aacute;sicas.

La gl&aacute;ndula mamaria y el gen homeobox Otx1.

Olfactory neuroblastoma is a rare tumor arising from the basal layer of the olfactory epithelium in the superior recesses of the nasal cavity. The rarity of this tumor, and the difficulties in culturing tumor cells has limited the generation of conventional cytogenetic data, whereas consistent results have been obtained by recent molecular methods. We report the results of an array-based comparative genomic hybridization analysis (a-CGH) obtained on 11 samples from 10 subjects: 8 primary and 3 relapsed tumors. In one patient, both the primary and relapsed tumors were available. Our results on chromosome imbalances highlight the highly heterogeneous presentation: six of eleven samples showed multiple numerical changes and very few structural ones, while four samples showed an opposite pattern; one sample out of eleven showed no imbalances. We did not reach firm evidence of any recurrent specific imbalances either at level of entire chromosomes or chromosome segments. A review of the literature indicates a number of recurrent gains, and losses, mostly not confirmed by our results. Gain of chromosome 19 was the only correspondence with literature data concerning an entire chromosome, and most segmental gains and losses found in our cohort of patients were different from those indicated in the literature: the only similarities concerned the gain of 20q13 and the loss of segments of chromosomes 15 and 22.

Comparative genomic hybridization on microarray (a-CGH) in olfactory neuroblastoma: Analysis of ten cases and review of the literature.

The HeLa cell line is one of the most popular cell lines in biomedical research, despite its well-known chromosomal instability. We compared the genomic and transcriptomic profiles of 4 different HeLa batches and showed that the gain and loss of genomic material varies widely between batches, drastically affecting basal gene expression. Moreover, different pathways were activated in response to a hypoxic stimulus. Our study emphasizes the large genomic and transcriptomic variability among different batches, to the point that the same experiment performed with different batches can lead to distinct conclusions and irreproducible results. The HeLa cell line is thought to be a unique cell line but it is clear that substantial differences between the primary tumour and the human genome exist and that an indeterminate number of HeLa cell lines may exist, each with a unique genomic profile. 

High variability of genomic instability and gene expression profiling in different HeLa clones.

Shwachman-Diamond syndrome (SDS) (OMIM 260400) is a rare autosomal recessive disease characterized by exocrine pancreatic insufficiency, skeletal, and hematological abnormalities and bone marrow (BM) dysfunction. Mutations in the SBDS gene cause SDS. Clonal chromosome anomalies are often present in BM, i(7)(q10) and del(20q) being the most frequent ones. We collected 6 SDS cases with del(20q): a cluster of imprinted genes, including L3MBTL1 and SGK2 is present in the deleted region. Only the paternal allele is expressed for these genes. Based on these data, we made the hypothesis that the loss of this region, in relation to parental origin of deletion, may be of relevance for the hematological phenotype. By comparing hematological data of our 6 cases with a group of 20 SDS patients without evidence of del(20q) in BM, we observed a significant difference for Hb levels (P < 0.012), and a difference slightly above the significance level for RBC counts (P < 0.053): in both cases the values were higher in patients with del(20q). We also report preliminary evidence for an increased number of BFU-E colonies in cases with paternal deletion, data on the presence of the deletion in colonies and in mature circulating lymphocytes. © 2016 Wiley Periodicals, Inc.

Parental origin of the deletion del(20q) in Shwachman-Diamond patients and loss of the paternally derived allele of the imprinted L3MBTL1 gene.

Two chromosome anomalies are frequent in the bone marrow (BM) of patients with Shwachman-Diamond syndrome (SDS): an isochromosome of the long arm of chromosome 7, i(7)(q10), and an interstitial deletion of the long arm of chromosome 20, del(20)(q). These anomalies are associated with a lower risk of developing myelodysplasia (MDS) and/or acute myeloid leukemia. The chromosome anomalies may be due to an SDS-specific karyotype instability, reflected also by anomalies that are not clonal, but found in single cells in the BM or in peripheral blood (PB).

Novel recurrent chromosome anomalies in Shwachman-Diamond syndrome.

OTX Homeobox genes are involved in embryonic morphogenesis and in the development of olfactory epithelium in adult. Mutations occurring in the OTX genes are reported to be associated to tumorigenisis in human. No reports correlate the expression of OTX genes and neoplasms of the nasal cavity. Thus, through immunohistochemical and Real-time PCR analysis we investigated OTX1 and OTX2 expression in the more frequent types of nasal and sinonasal tumours. Variable expression of both genes were found in normal sinonasal mucosa and in tumours. Interestingly, no expression of both OTX genes were detected in sinonasal intestinal-type adenocarcinomas; only OTX1 was found in non-intestinal-type adenocarcinomas and OTX2 was selectively expressed in olfactory neuroblastomas. In conclusion, OTX1 and OTX2 genes might have a role in the pathogenesis of different types of sinonasal neoplasms.

Article	Year
Different real time PCR approaches for the fine quantification of SNP's alleles in DNA pools: assays development, characterization and pre-validation. Journal of biochemistry and molecular biology\| PubMed ID: 16202235	2005
Establishment and study of different real-time polymerase chain reaction assays for the quantification of cells with deletions of chromosome 7. The Journal of molecular diagnostics : JMD\| PubMed ID: 16645208	2006
The mammary gland and the homeobox gene Otx1. The breast journal\| PubMed ID: 21050313	2010
Comparative genomic hybridization on microarray (a-CGH) in olfactory neuroblastoma: Analysis of ten cases and review of the literature. Genes, chromosomes & cancer\| PubMed ID: 26355525	2015
High variability of genomic instability and gene expression profiling in different HeLa clones. Scientific reports\| PubMed ID: 26483214	2015
Parental origin of the deletion del(20q) in Shwachman-Diamond patients and loss of the paternally derived allele of the imprinted L3MBTL1 gene. Genes, chromosomes & cancer\| PubMed ID: 27553422	2017
Novel recurrent chromosome anomalies in Shwachman-Diamond syndrome. Pediatric blood & cancer\| PubMed ID: 28130858	2017
OTX1 and OTX2 as possible molecular markers of sinonasal carcinomas and olfactory neuroblastomas. European journal of histochemistry : EJH\| PubMed ID: 28348423	2017

Francesco Pasquali

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