Nonclonal Chromosomal Aberrations Induced by Anti-Tumoral Regimens in Childhood Cancer

Mesa, Reyes López de; Sierrasesúmaga, Luis; Calasanz, Marı́a José; Ceráin, Adela López de

doi:10.1016/s0165-4608(00)00236-3

Cited by 13 publications

(6 citation statements)

References 18 publications

(30 reference statements)

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“…An abnormal clone could be a transient finding, especially when it presents as a small clone, 29 or a clone developing during or immediately following chemotherapy 30 or stem-cell transplant. 31 Bone marrow repair capacity and body immunosurveillance may have key roles in suppressing abnormal clones and clearing abnormal clones from the bone marrow.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of newly emerged isolated del(20q) in patients following cytotoxic therapies

Yin

Peng

et al. 2015

Modern Pathology

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Deletion 20q is a common chromosomal abnormality in myeloid neoplasms. Detection of del(20q) in patients following cytotoxic therapies raises concerns for an emerging therapy-related myeloid neoplasm. In this study, we identified 92 patients who acquired isolated del(20q) in their bone marrow following cytotoxic therapies for malignant neoplasms. Seventy-six patients showed interstitial and sixteen patients showed terminal 20q deletion. The median interval from prior cytotoxic therapies to detection of del(20q) was 58 months (range, 5-213 months). With a median follow-up of 23 months (range, 1-183 months), 21 (23%) patients developed therapy-related myeloid neoplasm and 71 (77%) patients did not. In patients who developed therapy-related myeloid neoplasm, del(20q) presented in a higher percentage of metaphases (60 vs 25%, Po 0.0001); persisted for a longer period of time (24 vs 10 months, P = 0.0487); and was more often a terminal deletion (33 vs 13%, P = 0.0006) compared with patients who did not develop therapy-related myeloid neoplasm. Clonal evolution was only detected in patients with therapy-related myeloid neoplasm (4 patients, 19%). We conclude that del(20q) emerging after cytotoxic therapy represents an innocuous finding in more than two-thirds of patients. In patients who develop a therapy-related myeloid neoplasm, del(20q) often involves a higher percentage of metaphases, persists longer and more frequently is a terminal rather than an interstitial deletion.

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Section: Discussionmentioning

confidence: 99%

Clinical significance of newly emerged isolated del(20q) in patients following cytotoxic therapies

Yin

Peng

et al. 2015

Modern Pathology

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“…Some CCA can be a transient finding, especially when the CCA emerges during or immediately following cytotoxic therapies (including chemotherapy and SCT); these transient CCAs are unlikely associated with t‐MDS/AML In a case series of acquired isolated del(7q) following cytotoxic therapies, among 27 patients who had at least 1 follow‐up cytogenetics study, del(7q) was persistent in 15 patients and was transient in 12 patients. Of note, 13 of 15 (87%) patients with persistent del(7q) were either diagnosed with t‐MDS at the time of del(7q) detection or developed t‐MDS during the follow‐up.…”

Section: Ccaus Emerging After Cytotoxic Therapiesmentioning

confidence: 99%

How I investigate Clonal cytogenetic abnormalities of undetermined significance

Tang

Medeiros

Wang

2018

Int J Lab Hematology

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Myelodysplastic syndromes are a group of hematopoietic stem cell diseases characterized by cytopenia(s), morphological dysplasia, and clonal hematopoiesis. In some patients, the cause of cytopenia(s) is uncertain, even after thorough clinical and laboratory evaluation. Evidence of clonal hematopoiesis has been used to support a diagnosis of myelodysplastic syndrome in this setting. In patients with cytopenia(s), the presence of clonal cytogenetic abnormalities, except for +8, del(20q) and -Y, can serve as presumptive evidence of myelodysplastic syndrome. Recent advances in next-generation sequencing have detected myeloid neoplasm-related mutations in patients who do not meet the diagnostic criteria for myelodysplastic syndrome. Various terms have been adopted to describe these cases, including clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). Similarly, studies have shown that certain chromosomal abnormalities, including ones commonly detected in myelodysplastic syndrome, may not be associated necessarily with an underlying myelodysplastic syndrome. These clonal cytogenetic abnormalities of undetermined significance (CCAUS) are similar to CHIP and CCUS. Here, we review the features of CCAUS, distinguishing CCAUS from clonal cytogenetic abnormalities associated with myelodysplastic syndrome, and the potential impact of CCAUS on patient management.

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“…There are several studies showing that chemotherapy (CT)/RT has a genotoxic effect on somatic cells from HL patients [17,20,[35][36][37][38][39][40]. Smith and colleagues [35] detected the genotoxic effects induced by MOPP/RT treatment through painting of chromosome 4 in lymphocytes from patients who were treated 12 to 24 years before the study.…”

Section: Impact Of Anticancer Therapy In Non-cancerous Somatic Cells mentioning

confidence: 99%

Non-Clonal Chromosome Aberrations and Genome Chaos in Somatic And Germ Cells from Patients and Survivors of Hodgkin Lymphoma, Induced by Anticancer Treatment

Frias¹,

Ramos²,

Salas-Labadía³

et al. 2018

Preprint

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Anticancer regimens for Hodgkin lymphoma (HL) patients include highly genotoxic drugs that have been very successful in killing tumor cells and providing a 90% disease-free survival at five years. However, these treatments do not have a specific cell target, damaging both cancerous and normal cells. Thus, HL survivors have a high risk of developing new primary cancers, both hematologic and solid tumors, that have been related to treatment. Several studies have shown that after-treatment, HL patients and survivors present persistent chromosomal instability, including non-clonal chromosomal aberrations. The frequency and type of chromosomal abnormalities appear to depend on the type of therapy and the cell type examined. For example, MOPP chemotherapy affects hematopoietic and germ stem cells leading to long-term genotoxic effects and azoospermia, while ABVD chemotherapy affects transiently sperm cells, with most of the patients showing recovery of spermatogenesis. Both regimens have long-term effects in somatic cells, presenting non-clonal chromosomal aberrations and genomic chaos in a fraction of non-cancerous cells. This is a source of karyotypic heterogeneity that could eventually generate a more stable population acquiring clonal chromosomal aberrations and leading towards the development of a new cancer. 

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Nonclonal Chromosomal Aberrations Induced by Anti-Tumoral Regimens in Childhood Cancer

Cited by 13 publications

References 18 publications

Clinical significance of newly emerged isolated del(20q) in patients following cytotoxic therapies

Clinical significance of newly emerged isolated del(20q) in patients following cytotoxic therapies

How I investigate Clonal cytogenetic abnormalities of undetermined significance

Non-Clonal Chromosome Aberrations and Genome Chaos in Somatic And Germ Cells from Patients and Survivors of Hodgkin Lymphoma, Induced by Anticancer Treatment

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