A tumor profile in Down syndrome

Abstract

We conducted a review of cancers in Down syndrome (DS), because solid tumors are poorly understood in DS. Cancers are in excess in this condition because of the 20-fold excess of leukemias, whereas malignant solid tumors seem to be globally underrepresented as compared with those in the general population. However, among these tumors, some tumors are in excess: lymphomas, gonadal and extragonadal germ cell tumors, and possibly retinoblastomas and pancreatic and bone tumors. Neoplasms in excess are seen earlier, sometimes in fetal life (leukemias and testicular germ cell tumors) or neonatally (leukemias and lymphoma) and affect mainly male subjects. There seems to exist an excess of rare karyotypes. Other tumors are underrepresented, particularly neuroblastomas and nephroblastomas, in young children, and perhaps common epithelial tumors in adults. These observations suggest that DS has a particular tumor profile, with some tissues more affected by malignant diseases (hematopoietic tissue and germ cells) and others that seem to be protected (central and peripheral nervous system, renal tissue, and epithelial tissues). The mechanism is mainly genetic, but differences in exposure to exogenous agents compared with the general population must be kept in mind. These findings are of interest for the management of these patients and early detection of cancers. Better knowledge of this tumor profile could help us to understand the mechanisms of carcinogenesis and should be compared to the current knowledge of genes on chromosome 21.

Aneuploidy Affects Proliferation and Spontaneous Immortalization in Mammalian Cells

“…Consistent with this idea is the observation that the occurrence of acute lymphoblastic leukemia and acute megakaryoblastic leukemia is greatly increased in Down Syndrome patients (20). However, the incidence of many solid tumors in these individuals is only half of that in the normal population, raising the possibility that aneuploidy also restricts the formation of certain tumors (21,22).…”

Aneuploidy impairs hematopoietic stem cell fitness and is selected against in regenerating tissues in vivo

“…Mouse chromosome 16 is the closest wholechromosome homolog to human chromosome 21 and thus a model of DS. This model is of particular interest because individuals with DS often show perturbations in the hematopoietic lineage (Henry et al 2007;Choi 2008) and have a greatly increased risk of developing childhood leukemia (Satge et al 1998). Mouse chromosome 19 is the smallest mouse autosome, with homology mainly with human chromosomes 9, 10, and 11.…”

Are solid tumours different in children with Down's syndrome?

“…It also found a difference in organ site and histology distribution of solid neoplasms. 1 In adults this was confirmed in 3 subsequent epidemiologic studies on cancer incidence and on causes of death in DS conducted in Denmark, 2 Israel 3 and the United States, 4 showing a very low incidence of carcinomas while germ cell tumours were more frequent than in the general population. However, for children Ͻ15 years of age, these studies could not provide sufficient data.…”