Genome complexity in acute lymphoblastic leukemia is revealed by array-based comparative genomic hybridization

Strefford, Jonathan C.; Worley, Helen; Barber, Kerry E.; Wright, Sarah; Stewart, Adam R. M.; Robinson, Hazel M.; Bettney, G; Delft, Frederik W. van; Atherton, Mark; Davies, Teresa; Griffiths, Mike; Hing, Sandra; Ross, Fiona; Talley, Polly; Saha, Vaskar; Moorman, Anthony V.; Harrison, Christine J.

doi:10.1038/sj.onc.1210190

Cited by 92 publications

(83 citation statements)

References 44 publications

(36 reference statements)

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“…[18][19][20][21] Thus, it is clear that the triple trisomies are seen in a substantial proportion of relapses of high hyperdiploid ALLs, a finding that may question their favorable prognostic impact.…”

Section: Discussionmentioning

confidence: 99%

Relapsed childhood high hyperdiploid acute lymphoblastic leukemia: presence of preleukemic ancestral clones and the secondary nature of microdeletions and RTK-RAS mutations

et al. 2010

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Although childhood high hyperdiploid acute lymphoblastic leukemia is associated with a favorable outcome, 20% of patients still relapse. It is important to identify these patients already at diagnosis to ensure proper risk stratification. We have investigated 11 paired diagnostic and relapse samples with single nucleotide polymorphism array and mutation analyses of FLT3, KRAS, NRAS and PTPN11 in order to identify changes associated with relapse and to ascertain the genetic evolution patterns. Structural changes, mainly cryptic hemizygous deletions, were significantly more common at relapse (Po0.05). No single aberration was linked to relapse, but four deletions, involving IKZF1, PAX5, CDKN2A/B or AK3, were recurrent. On the basis of the genetic relationship between the paired samples, three groups were delineated: (1) identical genetic changes at diagnosis and relapse (2 of 11 cases), (2) clonal evolution with all changes at diagnosis being present at relapse (2 of 11) and (3) clonal evolution with some changes conserved, lost or gained (7 of 11), suggesting the presence of a preleukemic clone. This ancestral clone was characterized by numerical changes only, with structural changes and RTK-RAS mutations being secondary to the high hyperdiploid pattern.

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Section: Discussionmentioning

confidence: 99%

Relapsed childhood high hyperdiploid acute lymphoblastic leukemia: presence of preleukemic ancestral clones and the secondary nature of microdeletions and RTK-RAS mutations

et al. 2010

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“…The CDKN2A locus (9p21.3) contains three related genes (ARF, p15INK4b, and p16INK4a) that encode distinct tumor suppressor proteins, all of which have wellestablished roles in tumor suppression (38). Both the loss of heterozygosity and complete DNA deletion of CDKN2A are common occurrences in a wide range of tumors including melanoma (39), leukemias (40), and non -small cell lung cancer (41). The recurring amplification of ZNF217 (20q13.2) has also been identified in studies of breast cancer and ovarian carcinomas.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide DNA copy number predictors of lapatinib sensitivity in tumor-derived cell lines

Greshock

Cheng

Rusnak

et al. 2008

Molecular Cancer Therapeutics

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A common aim of pharmacogenomic studies that use genome-wide assays on panels of cancers is the unbiased discovery of genomic alterations that are associated with clinical outcome and drug response. Previous studies of lapatinib, a selective dual-kinase inhibitor of epidermal growth factor receptor (EGFR) and HER2 tyrosine kinases, have shown predictable relationships between the activity of these target genes and response. Under the hypothesis that additional genes may play a role in drug sensitivity, a predictive model for lapatinib response was constructed from genome-wide DNA copy number data from 24 cancer cell lines. An optimal predictive model which consists of aberrations at nine distinct genetic loci, includes gains of HER2, EGFR, and loss of CDKN2A. This model achieved an area under the receiver operating characteristic curve of f0.85 (80% confidence interval, 0.70 -0.98; P < 0.01), and correctly classified the sensitivity status of 8 of 10 head and neck cancer cell lines. This study shows that biomarkers predictive for lapatinib sensitivity, including the previously described copy number gains of EGFR and HER2, can be discovered using novel genomic assays in an unbiased manner. Furthermore, these results show the utility of DNA copy number profiles in pharmacogenomic studies. [Mol Cancer Ther 2008;7(4):935 -43]

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“…Array comparative genomic hybridization can also be used to detect the typical pattern of genomic imbalances associated with dic (9;20), (see refs. [13][14][15][16] but this technique can not be used to prove the dicentric nature of the rearrangement. Thus, at present, interphase FISH analyses are needed to identify all dic(9;20)-positive cases.…”

Section: Introductionmentioning

confidence: 99%

“…(see refs. [11][12][13][14][15][16] As this subtle abnormality easily escapes detection by conventional cytogenetics, being misclassified as monosomy 20 and/or deletion of 9p, [2][3][4][5] and that it may have a clinically important impact, other methods are definitely needed. As of yet, the dic(9;20) has not been shown to result in any gene fusion, rendering PCR-based methods unavailable for detection.…”

Section: Introductionmentioning

confidence: 99%

The frequency and prognostic impact of dic(9;20)(p13.2;q11.2) in childhood B-cell precursor acute lymphoblastic leukemia: results from the NOPHO ALL-2000 trial

et al. 2011

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The dic(9;20)(p13.2;q11.2) is reported to be present in B2% of childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL). However, it easily escapes detection by G-banding analysis and its true prevalence is hence unknown. We performed interphase fluorescence in situ hybridization analysesFin a three-step mannerFusing probes for: (i) CDKN2A at 9p21, (ii) 20p and 20q subtelomeres and (iii) cen9 and cen20. Out of 1033 BCP ALLs diagnosed from 2001 to 2006, 533 were analyzed; 16% (84/533) displayed 9p21 deletions, of which 30% (25/84) had dic(9;20). Thus, dic(9;20)-positivity was found in 4.7% (25/533), making it the third most common genetic subgroup after high hyperdiploidy and t(12;21)(p13;q22). The dic(9;20) was associated with a female predominance and an age peak at 3 years; 18/25 (72%) were allocated to non-standard risk treatment at diagnosis. Including cases detected by G-banding alone, 29 dic(9;20)-positive cases were treated according to the NOPHO ALL 2000 protocol. Relapses occurred in 24% (7/29) resulting in a 5-year event-free survival of 0.69, which was significantly worse than for t(12;21) (0.87; P ¼ 0.002) and high hyperdiploidy (0.82; P ¼ 0.04). We conclude that dic(9;20) is twice as common as previously surmised, with many cases going undetected by G-banding analysis, and that dic(9;20) should be considered a non-standard risk abnormality.

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Genome complexity in acute lymphoblastic leukemia is revealed by array-based comparative genomic hybridization

Cited by 92 publications

References 44 publications

Relapsed childhood high hyperdiploid acute lymphoblastic leukemia: presence of preleukemic ancestral clones and the secondary nature of microdeletions and RTK-RAS mutations

Relapsed childhood high hyperdiploid acute lymphoblastic leukemia: presence of preleukemic ancestral clones and the secondary nature of microdeletions and RTK-RAS mutations

Genome-wide DNA copy number predictors of lapatinib sensitivity in tumor-derived cell lines

The frequency and prognostic impact of dic(9;20)(p13.2;q11.2) in childhood B-cell precursor acute lymphoblastic leukemia: results from the NOPHO ALL-2000 trial

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