{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T05:20:31Z","timestamp":1697520031415},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2011,6,2]],"date-time":"2011-06-02T00:00:00Z","timestamp":1306972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To gain a better understanding of the mechanism of chromosomal translocations in cancer, we investigated the spatial proximity between <jats:italic>CBFB<\/jats:italic> and <jats:italic>MYH11<\/jats:italic> genes involved in inv(16)(p13q22) found in patients with acute myeloid leukemia. Previous studies have demonstrated a role for spatial genome organization in the formation of tumorigenic abnormalities. The nonrandom localization of chromosomes and, more specifically, of genes appears to play a role in the mechanism of chromosomal translocations. Here, two\u2010color fluorescence in situ hybridization and confocal microscopy were used to measure the interphase distance between <jats:italic>CBFB<\/jats:italic> and <jats:italic>MYH11<\/jats:italic> in hematopoietic stem cells (HSCs), where inv(16)(p13q22) is believed to occur, leading to leukemia development. The measured distances in HSCs were compared with mesenchymal stem cells, peripheral blood lymphocytes, and fibroblasts, as spatial genome organization is determined to be cell\u2010type specific. Results indicate that <jats:italic>CBFB<\/jats:italic> and <jats:italic>MYH11<\/jats:italic> are significantly closer in HSCs compared with all other cell types examined. Furthermore, the <jats:italic>CBFB\u2010MYH11<\/jats:italic> distance is significantly reduced compared with <jats:italic>CBFB<\/jats:italic> and a control locus in HSCs, although separation between <jats:italic>CBFB<\/jats:italic> and the control is \u223c70% of that between <jats:italic>CBFB<\/jats:italic> and <jats:italic>MYH11<\/jats:italic> on metaphase chromosomes. HSCs were also treated with fragile site\u2010inducing chemicals because both the genes contain translocation breakpoints within these regions. However, treatment with fragile site\u2010inducing chemicals did not significantly affect the interphase distance. Consistent with previous studies, our results suggest that gene proximity may play a role in the formation of cancer\u2010causing rearrangements, providing insight into the mechanism of chromosomal abnormalities in human tumors. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20896","type":"journal-article","created":{"date-parts":[[2011,6,3]],"date-time":"2011-06-03T13:02:22Z","timestamp":1307106142000},"page":"746-755","source":"Crossref","is-referenced-by-count":1,"title":["<i>CBFB<\/i> and <i>MYH11<\/i> in inv(16)(p13q22) of acute myeloid leukemia displaying close spatial proximity in interphase nuclei of human hematopoietic stem cells"],"prefix":"10.1002","volume":"50","author":[{"given":"Allison B.","family":"Weckerle","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhumita","family":"Santra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maggie C.Y.","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick P.","family":"Koty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuh\u2010Hwa","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,6,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1088845"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-10-59"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)01113-3"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81388-4"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00084a025"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/35036309"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-002-8429-3"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2007.08.005"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209268"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.502"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2005.08.032"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(98)01383-X"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6434"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.12.4537"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004120050394"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-04-1064"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.12.014"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.11.030"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8351518"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050547"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1178124"},{"key":"e_1_2_6_23_1","first-page":"335","article-title":"Preferred co\u2010localization of chromosome 8 and 21 in myeloid bone marrow cells detected by three dimensional molecular cytogenetics","volume":"24","author":"Manvelyan M","year":"2009","journal-title":"Int J Mol Med"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900912106"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2006.10.008"},{"key":"e_1_2_6_26_1","unstructured":"MitelmanF JohanssonB MertensF editors.2010. 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