A Case Report of Down Syndrome and Centroblastic Lymphoma

Satgé, Daniel; Tourneau, A. Le; Verger, J.-P; Lefort, Sophie; Geneix, A; Malet, P; Diébold, J; Vekemans, Michel

doi:10.1016/s0344-0338(96)80165-8

Cited by 16 publications

(12 citation statements)

References 17 publications

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“…It was striking that lymphomatous disorders were restricted to the Ts65, Ts2, Ts1Cje, and hTau genotypes (and a few PS1 mice that did not meet statistical significance). This restricted distribution suggests a relation to the occurrence of leukemias and lymphomas in HSA 21 (Patja et al, 2006; Satge et al, 1996; Smrcek et al, 2001; and Zipursky et al, 1992). However, no increase in the incidence of lymphoma was found in APP overexpressing mice compared to ntg mice.…”

Section: Resultsmentioning

confidence: 90%

Systemic pathology in aged mouse models of Down's syndrome and Alzheimer's disease

Levine

Saltzman

Levy

et al. 2009

Experimental and Molecular Pathology

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Down's syndrome (DS) in humans is caused by trisomy of chromosome 21 (HSA 21). DS patients have a variety of pathologies, including mental retardation and an unusually high incidence of leukemia or lymphoma such as megakaryocytic leukemia. Individuals with DS develop the characteristic neuropathological hallmarks of Alzheimer's disease (AD) in early adulthood, generally by the fourth decade of life. There are several mouse models of DS that have a segmental trisomy of mouse chromosome 16 (MMU 16) with triplicated genes orthologous to HSA 21. These mice display neurodegeneration similar to DS. Although brain pathology in DS models is known, little information is available about other organs. We studied the extraneural pathology in aged DS mice (Ts65Dn, Ts2 and Ts1Cje aged 8 to 24 months) as well as other mouse models of neurodegeneration, including presenilin (PS), amyloid-β precursor protein (APP), and tau (hTau and JNPL) transgenic mice. An increased incidence of peripheral amyloidosis, positive for amyloid A (AA) but not amyloid-β peptide (Aβ), was found in APP over-expressing and tauopathic mice as compared to nontransgenic (ntg) littermates or to DS mouse models. A higher incidence of lymphoma was found in the DS models, including Ts1Cje that is trisomic for a small segment of MMU 16 not including the App gene, but not in the APP over-expressing mice, suggesting that high APP expression is not the cause of lymphoma in DS. The occurrence of lymphomas in mouse DS models is of interest in relation to the increased incidence of malignant conditions in human DS.

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Section: Resultsmentioning

confidence: 90%

Systemic pathology in aged mouse models of Down's syndrome and Alzheimer's disease

Levine

Saltzman

Levy

et al. 2009

Experimental and Molecular Pathology

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“…[2][3][4] However, large population-based and/or tumor registries have shown that solid tumors occur significantly less frequently in DS children and adults in comparison with individuals without trisomy 21. Among 2814 individuals from different age groups with DS registered in a Danish study, only 24 cases of solid tumors were identified, whereas 47.7 cases would have been expected.…”

mentioning

confidence: 99%

Down Syndrome and Malignancies: A Unique Clinical Relationship

Xavier

Taub

2009

The Journal of Molecular Diagnostics

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The patterns of malignancies in Down syndrome (DS) are unique and highlight the relationship between chromosome 21 and cancer. DS children have a ϳ10-to 20-fold higher risk for developing acute lymphoblastic leukemia and acute myeloid leukemia (AML), as compared with non-DS children , although they do not have a uniformly increased risk of developing solid tumors. DS children with acute lymphoblastic leukemia frequently experience higher levels of treatment-related toxicity and inferior event-free survival rates , as compared with non-DS children. DS children also develop AML with unique features and have a 500-fold increased risk of developing the AML subtype , acute megakaryocytic leukemia (AMkL; M7). Nearly 10% of DS newborns are diagnosed with a variant of AMkL , the transient myeloproliferative disorder , which can resolve spontaneously without treatment; event-free survival rates for DS patients with AMkL ranges from 80% to 100% , in comparison with <30% for non-DS children with AMkL. In addition , somatic mutations of the GATA1 gene have been detected in nearly all DS TMD and AMkL cases and not in leukemia cases in non-DS children. 1 Based on the prevalence and recognition of DS individuals in the general population, considerable resources have been directed toward studying the various phenotypic features of DS individuals including learning disabilities, congenital heart disease, early onset Alzheimer's disease, and high risk of developing leukemia.Although DS children have an increased risk of developing acute leukemias, there is no increased risk of solid tumors in DS individuals. These discrepancies highlight the relationship between chromosome 21 and cancer, and they will be the subject of this review.

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“…Children with DS have a ~10- to 20-fold higher risk of developing acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), as compared with non-DS children [1]. Certain solid tumors including lymphomas, retinoblastomas, and testicular germ cell tumors, have been reported in individuals with DS [2,3,4]. However, children with DS do not have a uniformly increased risk of developing solid tumors.…”

Section: Introductionmentioning

confidence: 99%

Down’s Syndrome and Triple Negative Breast Cancer: A Rare Occurrence of Distinctive Clinical Relationship

Dey

Krie

Klein

et al. 2017

IJMS

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Down’s syndrome (DS), the most common genetic cause of significant intellectual disability in children and adults is caused by the trisomy of either all or a part of human chromosome 21 (HSA21). Patients with DS mostly suffer from characteristic tumor types. Although individual patients of DS are at a higher risk for acute leukemia and testicular cancers, other types of solid tumors including breast cancers are mostly uncommon and have significantly lower-than-expected age-adjusted incidence rates. Except for an increased risk of retinoblastomas, and lymphomas, the risk of developing solid tumors has been found to be lower in both children and adults, and breast cancer was found to be almost absent (Hasle H., The Lancet Oncology, 2001). A study conducted in the United States found only one death when 11.65 were expected (Scholl T et al., Dev Med Child Neurol. 1982). A recent study examined mammogram reports of women with DS treated in the largest medical facility specifically serving adults with DS in the United States. It was found that only 0.7% women with DS had been diagnosed with breast cancers (Chicoine B et al., Intellect Dev Disabil. 2015). Here we describe a case of breast cancer in a 25-year-old patient with DS. The disease was presented as lymph node positive carcinoma with alterations of tumor suppressor genes characteristic to the triple negative breast cancer subtype. Comprehensive Genomic Profiling (CGP) revealed a wild-type status for BRCA1. The CGP report showed a frameshift mutation, A359fs*10 of the tumor suppressor gene INPP4B and another frameshift mutation, R282fs*63 of tumor suppressor gene TP53 in the tumor biopsy as characteristically found in triple-negative breast cancers. The VUS (Variance of Unknown Significance) alteration(s) were identified in ASXL1 (L1395V), NTRK1 (G18E), DDR2 (I159T), RUNX1 (amplification), ERG (amplification), SOX2 (T26A), FAM123B (G1031D), and HNF1A (A301T). Bonafide cancer-related genes of chromosome 21 amplified in the patient’s tumor are RUNX1 and ERG genes. After the completion of the radiation, the patient was placed on everolimus which was based on the result of her CGP report. Thus, post-mastectomy radiation therapy was completed with a recommendation for everolimus for one year. During the time of writing of this report, no metastatic lesions were identified. The patient currently has no evidence of disease.

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A Case Report of Down Syndrome and Centroblastic Lymphoma

Cited by 16 publications

References 17 publications

Systemic pathology in aged mouse models of Down's syndrome and Alzheimer's disease

Systemic pathology in aged mouse models of Down's syndrome and Alzheimer's disease

Down Syndrome and Malignancies: A Unique Clinical Relationship

Down’s Syndrome and Triple Negative Breast Cancer: A Rare Occurrence of Distinctive Clinical Relationship

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