Three distinct subgroups of hypodiploidy in acute lymphoblastic leukaemia

Harrison, Christine J.; Moorman, Anthony V.; Broadfield, Zoë J.; Cheung, Kan Luk; Harris, Rachel L.; Jalali, G. Reza; Robinson, Hazel M.; Barber, Kerry E.; Richards, Susan; Mitchell, Christopher; Eden, Tim; Hann, Ian; Hill, F. G. H.; Kinsey, Sally; Gibson, Brenda; Lilleyman, J S; Vora, Ajay; Goldstone, Anthony H.; Franklin, Ian M.; Durrant, Ian; Martineau, Mary

doi:10.1111/j.1365-2141.2004.04948.x

Cited by 205 publications

(260 citation statements)

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“…Cancer type incidence. Information on incidence of cancer types in the population was derived from the SEER database (Surveillance, Epidemiology, and End Results program) 8 ; further detailed information on different subgroups of cancer types (central nervous system tumours and subgroups of medulloblastoma, ependymoma, and ALL) was transferred from cancer type-specific publications [75][76][77][78][79] . Survival data are based on information from the German Childhood Cancer Registry 80 .…”

Section: Methodsmentioning

confidence: 99%

The landscape of genomic alterations across childhood cancers

Gröbner¹,

Worst²,

Weischenfeldt³

et al. 2018

Nature

1,235

1,156

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The landscape of genomic alterations across childhood cancers a list of authors and affiliations appears at the end of the paper. OPENPan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7-8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.Cure rates for childhood cancers have increased to about 80% in recent decades, but cancer is still the leading cause of death by disease in the developed world among children over one year of age 1,2 . Furthermore, many children who survive cancer suffer from long-term sequelae of surgery, cytotoxic chemotherapy, and radiotherapy, including mental disabilities, organ toxicities, and secondary cancers 3 . A crucial step in developing more specific and less damaging therapies is the unravelling of the complete genetic repertoire of paediatric malignancies, which differ from adult malignancies in terms of their histopathological entities and molecular subtypes 4 . Over the past few years, many entityspecific sequencing efforts have been launched, but the few paediatric pan-cancer studies thus far have focused only on mutation frequencies, germline predisposition, and alterations in epigenetic regulators [4][5][6] .We have carried out a broad exploration of cancers in children, adolescents, and young adults, by incorporating small mutations and copy-number or structural variants on somatic and germline levels, and by identifying putative cancer genes and comparing them to those previously reported in adult cancers by The Cancer Genome Atlas (TCGA) 7 . We have also examined mutational signatures and potential drug targets. The compendium of genetic alterations presented here is available to the scientific community at http://www.pedpancan.com.This integrative analysis includes 24 types of cancer and covers all major childhood cancer entities, many of which occur exclusively in children 8 (Fig. 1, Supplementary Table 1). Ninety-five per cent of the patients in this study were diagnosed during childhood or adolescence (aged 18 years or younger) and 5% as young adults (up to 25 years) (Extended Data ...

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Section: Methodsmentioning

confidence: 99%

The landscape of genomic alterations across childhood cancers

Gröbner¹,

Worst²,

Weischenfeldt³

et al. 2018

Nature

1,235

1,156

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“…2,6 All cases in the present study harbored complete LOH for chromosomes that were not retained. This could correspond either to the majority of chromosomes being monosomies, i.e., all disomic chromosomes being UPIDs in a duplicated clone.…”

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confidence: 65%

“…Chromosome 21 was retained in two copies (heterodisomy) in all nearhaploid cases, followed by retention of both copies of chromosomes 14 (6/8; 75%), X/Y (5/8; 63%), 18 (3/8 cases each; 38%), and 8 and 10 (2/8 each; 25%) ( agreeing well with previous investigations. 2,6 Thus, both the near-haploid and the HoL cases displayed a nonrandom retention of both parental copies of chromosomes X/Y, 14, 18, and 21. The reason why some chromosomes are preferentially heterodisomic is unknown.…”

mentioning

confidence: 96%

“…2,5,6 In childhood ALL, both near-haploidy and HoL are associated with a dismal prognosis, with a 3-year event-free survival rate of 30%; adult patients with HoL also have extremely poor overall survival rates of only 20-30%. 2,3,7,8 Because of the rarity of near-haploid/HoL ALL, relatively few studies have focused on these genetic subgroups and no SNP array data have been reported to date. Considering the poor prognosis of these cases, further investigations are needed to increase our understanding of the pathogenetic impact of massive chromosomal loss in ALL.…”

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confidence: 99%

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Loss of chromosomes is the primary event in near-haploid and low-hypodiploid acute lymphoblastic leukemia

et al. 2012

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Loss of chromosomes is the primary event in near-haploid and low hypodiploid acute lymphoblastic leukemia. Link to publication Citation for published version (APA): Safavi, S., Forestier, E., Golovleva, I., Barbany, G., Hansén Nord, K., Moorman, A. V., ... Paulsson, K. (2013). Loss of chromosomes is the primary event in near-haploid and low hypodiploid acute lymphoblastic leukemia. Leukemia, 27(1), 248-250. DOI: 10.1038/leu.2012 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal The majority of patients with hypodiploid ALL have 45 chromosomes; near-haploidy and HoL are very rare, comprising less than 1% of B-cell precursor (BCP) ALL. 2,4 Near-haploid ALL is seen primarily in children and adolescents, although some adult cases have been reported, whereas HoL occurs at all ages. 4 Cases usually have an early pre-B

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“…The other types of hypodiploidy are much rarer, and they include nearhaploidy (24-29 chromosomes), low-hypodiploidy (30-39 chromosomes) and high-hypodiploidy (40-44 chromosomes) [25]. About 1% of children (< 15 years) with ALL have a near haploid karyotype.…”

Section: A) Primary Chromosomal Abnormalities (I) Chromosomal Translomentioning

confidence: 99%

Routine Cytogenetic Analysis of Chromosome Abnormalities in Acute Lymphoblastic Leukemia

Meng¹

2015

Int Jour of Biomed Res

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Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Acquired chromosomal and genetic abnormalities have been used to define distinct biological and clinical subtypes of ALL. These aberrations have been shown to be associated with patient outcome and are used to direct therapy. Conventional cytogenetics analysis (CCA) is currently the gold standard to detect chromosome abnormalities in hematological malignancies. In this review we briefly describe the CCA methodology, advantages and limitations of CCA, the main chromosomal abnormalities and their prognostic significance in ALL.

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Three distinct subgroups of hypodiploidy in acute lymphoblastic leukaemia

Cited by 205 publications

References 19 publications

The landscape of genomic alterations across childhood cancers

The landscape of genomic alterations across childhood cancers

Loss of chromosomes is the primary event in near-haploid and low-hypodiploid acute lymphoblastic leukemia

Routine Cytogenetic Analysis of Chromosome Abnormalities in Acute Lymphoblastic Leukemia

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