title: Disease-associated patterns of disomic chromosomes in hyperhaploid neoplasms.
abstract: The chromosome number of human tumors varies widely, from near-haploidy to more than decaploidy. Overt hyperhaploid (24-34 chromosomes) tumors constitute a small minority (0.2-0.3% of cytogenetically investigated lesions), but occur in many different disease entities. In these karyotypes, most chromosomes are present in one copy; one or a few chromosomes are disomic. Published reports on 141 strictly hyperhaploid tumors, supplemented with nine previously unpublished cases, were used for evaluating the pattern of disomic chromosomes. Only one tumor type, acute lymphoblastic leukemia (ALL), was sufficiently common (n = 75) to allow proper evaluation; other neoplasms were lumped together in as reasonably logical groups as possible, including 10 myeloid leukemias (ML), nine plasma cell neoplasms (PCN), 13 chondrosarcomas (CS), 11 soft tissue tumors (STT), nine adeno- or squamous cell carcinomas (ASC), and eight tumors of the nervous system (TNS); the remaining 15 tumors could not be grouped. It was evident that the pattern of disomies is nonrandom. Moreover, unique signatures for each tumor group were detected. Among ALL, most disomies were independent of age and gender, except for disomy 10, which was overrepresented in females. Chromosome 21 was invariably disomic, whereas chromosome 17 was always monosomic. The most frequent disomies were two gonosomes in ML, chromosomes 7, 9, 11, 3, 18, and 19 in PCN, 7, 5, 20, 19, and 21 in CS, 20 in STT, 7 in ASC, and 1, 7, and 9 in TNS. Chromosome 1 was often partially disomic, due to unbalanced structural rearrangements, with segment 1q21-31 in common. Doubling of the hyperhaploid clone was found in at least one-third of the cases, apart from in ML where only one of 10 cases showed chromosome doubling. The present findings indicate that retention of disomy for some chromosomes is pathogenetically important and that the chromosome(s) maintained in two copies is related to cell type or histological context.
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden. nils.mandahl@med.lu.se
authors.forename: Nils
authors.initials: N
authors.lastname: Mandahl
authors.forename: Bertil
authors.initials: B
authors.lastname: Johansson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
authors.forename: Felix
authors.initials: F
authors.lastname: Mitelman
mesh_terms: D059786:Abnormal Karyotype; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D020440:Gene Duplication; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*; D011003:Ploidies