Cytogenetic deletion maps of hematologic neoplasms: Circumstantial evidence for tumor suppressor Loci

Abstract Research in oncogenetics has led to the identification of two major classes of tumor‐associated genes, oncogenes and tumor suppressor genes. In a wide variety of solid tumor types, mutations of both groups of genes have been implicated in the tumorigenic process. In hematologic neoplasms, on the other hand, most attention has focused on illegitimate activation of oncogenes, e.g., deregulation leading to disturbed transcriptional activity and structural rearrangements resulting in hybrid genes. Whether loss or mutational inactivation of tumor suppressor genes also plays an essential role in the genesis of tumors of the hematopoietic system has received less attention. Because such inactivation can be the result of karyotypically detectable loss of chromosomal material, cytogenetic studies may prove helpful in pinpointing genomic sites that harbor tumor suppressor genes. The present study is based on a total of 12,473 cytogenetically abnormal hematologic neoplasms reported in the literature to date. Among these, we selected the 6,422 cases with sole clonal chromosomal abnormalities in order to include only aberrations of importance in the genesis, rather than in the progression, of these neoplasms. All tumors with monosomies or structural abnormalities resulting in loss of chromosomal material were compiled, and for every such structural aberration, i.e., deletion, unbalanced translocation, isochromosome, and ring chromosome, the chromosome bands lost were ascertained. This cytogenetic deletion mapping revealed that the most commonly lost chromosomes were Y and 7 in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and chronic myeloproliferative disorders (MPD); X, Y, 7, 20, and 21 in acute lymphocytic leukemia (ALL); X, Y, and 17 in chronic lymphoproliferative disorders (LPD); and X and Y in non‐Hodgkin's lymphoma (NHL). Chromosome segments/bands lost due to unbalanced structural abnormalities in at least 5% of the cases were 5q13ndash;33. 7q22ndash;36, 9q13ndash;31, 11q23ndash;25, 12p12ndash;13, 17p11ndash;13, and 20q11ndash;13 in AML; 5q13ndash;35 and 20q11ndash;13 in MDS; 5q22ndash;23, 7q22, 13q12ndash;22, 17p11ndash;13, and 20q11ndash;13 in MPD; 6q15ndash;27, 9p11ndash;24, 12p12ndash;13, and 19p13 in ALL; 6q16ndash;27, 11q21ndash;25, 13q13ndash;14, and 14q32 in LPD; and 6q21ndash;27, 11q13ndash;25, and 14q24ndash;32 in NHL. Based on these findings, three conclusions can be drawn. First, there is no good correspondence between total and partial monosomies, the only exception being ndash;7 and 7qndash;, both of which are common in myeloid neoplasms. This indicates different pathogenetic effects of total and partial losses. Second, clinically and biologically related hematologic malignancies display similarities in chromosomal material lost. Third, molecular studies on genetic loss have, to date, focused on deletions involving the long arms of chromosomes 5, 6, 7, 13, and 20 and the short arms of chromosomes 9 and 17. The cytogenetic deletion maps presented herein indicate that there are also other genomic sites of interest for further molecular analyses. © 1993 Wiley‐Liss, Inc.