{"id":{"repo_id":"soton","oai_identifier":"oai:eprints.soton.ac.uk:161483"},"canonical_url":"https://search.dev.ndltd.org/etd/soton/oai:eprints.soton.ac.uk:161483","repository":{"repo_id":"soton","name":"University of Southampton","base_url":"https://eprints.soton.ac.uk/cgi/oai2"},"display":{"title":"Acquired abnormalities of chromosome 21 in acute lymphoblastic leukaemia","abstract":"The intrachromosomal amplification of chromosome 21 (iAMP21) was identified<br/>as a novel and prognositically important acquired chromosomal abnormality in<br/>childhood acute lymphoblastic leukaemia (ALL). It is defined by multiple copies<br/>of the RUNX1 gene, as seen by fluorescence in situ hybridisation (FISH), localised<br/>to a single abnormal duplicated chromosome 21 [dup(21)]. The morphological<br/>form of this chromosome is highly variable between patients and currently the<br/>only reliable method of detection is FISH with probes to RUNX1. Studies of 48<br/>iAMP21 patients using detailed FISH techniques and array-based comparative<br/>genomic hybridisation highlighted an extensive region of chromosome 21<br/>involvement. A minimum common region of amplification, between 33.19 and<br/>39.80Mb, including RUNX1 was identified, together with a minimum common<br/>region of deletion, between 46.54 and 46.92Mb, in 100% and 77% of patients,<br/>respectively. This study established that there were unique patterns of imbalance,<br/>with evidence of deletions, inversions and amplification, displayed on the<br/>dup(21), between individual patients. This provided evidence of an abnormality<br/>that may have arisen from a breakage-fusion-bridge mechanism, possibly initiated<br/>by loss of a telomere. Results indicated that iAMP21 represents a distinct genetic<br/>subgroup of childhood ALL and is not secondary to a cryptic abnormality of<br/>chromosome 21. Two possible variant cases were identified both involving<br/>chromosome 15. The abnormality can be distinguished from other numerical<br/>abnormalities of chromosome 21 by exploiting the unique pattern of gain,<br/>amplification and deletion seen in these patients. This allowed for the<br/>development of diagnostic tests based on copy number using either FISH or<br/>multiplex ligation dependent probe amplification (MLPA), both of which<br/>successfully identified iAMP21 patients.","abstract_html":"The intrachromosomal amplification of chromosome 21 (iAMP21) was identified&lt;br/&gt;as a novel and prognositically important acquired chromosomal abnormality in&lt;br/&gt;childhood acute lymphoblastic leukaemia (ALL). It is defined by multiple copies&lt;br/&gt;of the RUNX1 gene, as seen by fluorescence in situ hybridisation (FISH), localised&lt;br/&gt;to a single abnormal duplicated chromosome 21 [dup(21)]. The morphological&lt;br/&gt;form of this chromosome is highly variable between patients and currently the&lt;br/&gt;only reliable method of detection is FISH with probes to RUNX1. Studies of 48&lt;br/&gt;iAMP21 patients using detailed FISH techniques and array-based comparative&lt;br/&gt;genomic hybridisation highlighted an extensive region of chromosome 21&lt;br/&gt;involvement. A minimum common region of amplification, between 33.19 and&lt;br/&gt;39.80Mb, including RUNX1 was identified, together with a minimum common&lt;br/&gt;region of deletion, between 46.54 and 46.92Mb, in 100% and 77% of patients,&lt;br/&gt;respectively. This study established that there were unique patterns of imbalance,&lt;br/&gt;with evidence of deletions, inversions and amplification, displayed on the&lt;br/&gt;dup(21), between individual patients. This provided evidence of an abnormality&lt;br/&gt;that may have arisen from a breakage-fusion-bridge mechanism, possibly initiated&lt;br/&gt;by loss of a telomere. Results indicated that iAMP21 represents a distinct genetic&lt;br/&gt;subgroup of childhood ALL and is not secondary to a cryptic abnormality of&lt;br/&gt;chromosome 21. Two possible variant cases were identified both involving&lt;br/&gt;chromosome 15. The abnormality can be distinguished from other numerical&lt;br/&gt;abnormalities of chromosome 21 by exploiting the unique pattern of gain,&lt;br/&gt;amplification and deletion seen in these patients. This allowed for the&lt;br/&gt;development of diagnostic tests based on copy number using either FISH or&lt;br/&gt;multiplex ligation dependent probe amplification (MLPA), both of which&lt;br/&gt;successfully identified iAMP21 patients.","abstract_has_math":false,"creators":["Robinson, Hazel M."],"institution":"University of Southampton","degree_name":"Ph.D.","degree_level":"doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Harrison, Christine J.","Moorman, Anthony"],"committee_chairs":[],"committee_members":[],"year":2008,"date_issued":"2008-06","date_published":"2008-06","updated_at":"2026-07-24T04:36:17Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Harrison, Christine J.","Moorman, Anthony"]},{"key":"dc:creator","label":"Author","values":["Robinson, Hazel M."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2008-06"]},{"key":"dc:date.issued","label":"Date","values":["2008-06"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Cancer Sciences (pre 2011 reorg)","School of Medicine"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Southampton"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://eprints.soton.ac.uk/161483/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Ph.D."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://eprints.soton.ac.uk/161483/1/PhD_Thesis_Hazel_Robinson.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The intrachromosomal amplification of chromosome 21 (iAMP21) was identified<br/>as a novel and prognositically important acquired chromosomal abnormality in<br/>childhood acute lymphoblastic leukaemia (ALL). It is defined by multiple copies<br/>of the RUNX1 gene, as seen by fluorescence in situ hybridisation (FISH), localised<br/>to a single abnormal duplicated chromosome 21 [dup(21)]. The morphological<br/>form of this chromosome is highly variable between patients and currently the<br/>only reliable method of detection is FISH with probes to RUNX1. Studies of 48<br/>iAMP21 patients using detailed FISH techniques and array-based comparative<br/>genomic hybridisation highlighted an extensive region of chromosome 21<br/>involvement. A minimum common region of amplification, between 33.19 and<br/>39.80Mb, including RUNX1 was identified, together with a minimum common<br/>region of deletion, between 46.54 and 46.92Mb, in 100% and 77% of patients,<br/>respectively. This study established that there were unique patterns of imbalance,<br/>with evidence of deletions, inversions and amplification, displayed on the<br/>dup(21), between individual patients. This provided evidence of an abnormality<br/>that may have arisen from a breakage-fusion-bridge mechanism, possibly initiated<br/>by loss of a telomere. Results indicated that iAMP21 represents a distinct genetic<br/>subgroup of childhood ALL and is not secondary to a cryptic abnormality of<br/>chromosome 21. Two possible variant cases were identified both involving<br/>chromosome 15. The abnormality can be distinguished from other numerical<br/>abnormalities of chromosome 21 by exploiting the unique pattern of gain,<br/>amplification and deletion seen in these patients. This allowed for the<br/>development of diagnostic tests based on copy number using either FISH or<br/>multiplex ligation dependent probe amplification (MLPA), both of which<br/>successfully identified iAMP21 patients."]},{"key":"dc:format","label":"Dc Format","values":["text"]},{"key":"dc:title","label":"Title","values":["Acquired abnormalities of chromosome 21 in acute lymphoblastic leukaemia"]}]}],"canonical_facts":{"dc:contributor.advisor":["Harrison, Christine J.","Moorman, Anthony"],"dc:creator":["Robinson, Hazel M."],"dc:date":["2008-06"],"dc:date.issued":["2008-06"],"dc:description.abstract":["The intrachromosomal amplification of chromosome 21 (iAMP21) was identified<br/>as a novel and prognositically important acquired chromosomal abnormality in<br/>childhood acute lymphoblastic leukaemia (ALL). It is defined by multiple copies<br/>of the RUNX1 gene, as seen by fluorescence in situ hybridisation (FISH), localised<br/>to a single abnormal duplicated chromosome 21 [dup(21)]. The morphological<br/>form of this chromosome is highly variable between patients and currently the<br/>only reliable method of detection is FISH with probes to RUNX1. Studies of 48<br/>iAMP21 patients using detailed FISH techniques and array-based comparative<br/>genomic hybridisation highlighted an extensive region of chromosome 21<br/>involvement. A minimum common region of amplification, between 33.19 and<br/>39.80Mb, including RUNX1 was identified, together with a minimum common<br/>region of deletion, between 46.54 and 46.92Mb, in 100% and 77% of patients,<br/>respectively. This study established that there were unique patterns of imbalance,<br/>with evidence of deletions, inversions and amplification, displayed on the<br/>dup(21), between individual patients. This provided evidence of an abnormality<br/>that may have arisen from a breakage-fusion-bridge mechanism, possibly initiated<br/>by loss of a telomere. Results indicated that iAMP21 represents a distinct genetic<br/>subgroup of childhood ALL and is not secondary to a cryptic abnormality of<br/>chromosome 21. Two possible variant cases were identified both involving<br/>chromosome 15. The abnormality can be distinguished from other numerical<br/>abnormalities of chromosome 21 by exploiting the unique pattern of gain,<br/>amplification and deletion seen in these patients. This allowed for the<br/>development of diagnostic tests based on copy number using either FISH or<br/>multiplex ligation dependent probe amplification (MLPA), both of which<br/>successfully identified iAMP21 patients."],"dc:format":["text"],"dc:identifier.uri":["https://eprints.soton.ac.uk/161483/1/PhD_Thesis_Hazel_Robinson.pdf"],"dc:publisher.department":["Cancer Sciences (pre 2011 reorg)","School of Medicine"],"dc:publisher.institution":["University of Southampton"],"dc:relation.isreferencedby":["https://eprints.soton.ac.uk/161483/"],"dc:title":["Acquired abnormalities of chromosome 21 in acute lymphoblastic leukaemia"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["Ph.D."]},"updated_at":"2026-07-24T04:36:17Z"}