Mutation Research 525 (2003) 103–107 Y chromosome instability in lymphoproliferative disorders Silvina M. Richard a,∗ , Sakari Knuutila b , Päivi Peltomäki c , Martha S. Bianchi a , Néstor O. Bianchi a a Instituto Multidisciplinario de Biolog´ ıa Celular (IMBICE), Calle 526 e/10 y 11, CC 403, 1900 La Plata, Argentina b Department of Pathology and Medical Genetics, Haartman Institute and Helsinki, University Central Hospital, Helsinki, Finland c Department of Medical Genetics, University of Helsinki, Helsinki, Finland Received 30 September 2002; received in revised form 22 November 2002; accepted 8 January 2003 We recently tested for deletions 17 loci of the azoospermia factor (AZF) gene family in non-tumor and tumor tissues of 17 males having testicular ma- lignancies. Thirteen of the cases (76%) had deletions in 1–8 AZF loci conforming three different models that usually coexist in the Y chromosomes of the same donor: “a” or -/-, deletion of a given AZF fragment in normal and cancer tissues; “b” or +/-, fragment deletion in cancer but not in normal tis- sues; and “c” or -/+, AZF deletion in normal but not in cancer cells. Moreover, no AZF deletions were detected in the Y chromosomes from fathers of the tumor cases or in the Y chromosomes from 80 normal males. From the above data it was concluded that: (i) non-tumor tissues from testicular cancer cases having Y-microdeletions were mosaics with two or more cell lineages characterized by the presence of Y chro- mosomes exhibiting lineage-specific AZF deletion patterns (an AZF deletion pattern is defined by the combination of models a–c in the different loci of a given Y chromosome; all Y chromosomes from a given lineage exhibit the same deletion pattern); (ii) monoclonal cell transformation followed by cell ex- ∗ Corresponding author. Tel.: +54-221-425-3320; fax: +54-221-425-3320. E-mail addresses: bianchi@satlink.com, bianchi@imbice.org.ar (S.M. Richard). pansion gives rise to testicular tumors showing the AZF deletion pattern of the cell lineage in which malignant transformation occurred; (iii) AZF deletion mosaicisms occurred very early in embryo develop- ment and were considered to be part of a broader phenomenon of genome instability producing suscep- tibility to testicular cancer [1]. Two out of the 17 cases of testicular cancers re- ported to have AZF deletions were testicular forms of non-Hodgkin lymphomas suggesting that Y chro- mosome instability may appear in malignancies other than seminoma and non-seminoma tumors [1]. Here, we present data on the analysis of AZF deletions in 27 additional cases of lymphoprolifera- tive disorders. Samples were taken from pre-treated patients and all donors gave informed consent for the study. Diagnoses are given in Tables 1 and 2 for each lymphoproliferative disorder. DNA samples in cases 1–10 (Table 1) were from peripheral blood (non-lymphoma DNA) and from lymph nodes (lym- phoma DNA). Non-lymphoma samples were negative for IGHJ/TCRB rearrangements, and for lymphoma cell infiltration as determined by immunocytochem- ical tests. On the other hand, with the exception of case 4, all other lymphoma samples showed IGHJ or TCRB rearrangements. The proportions of tumor cells in lymphoma specimens were over 70% in non-Hodgkin lymphomas and more than 10% in the Hodgkin case (patient 4, Table 1). 0027-5107/03/$ – see front matter © 2003 Elsevier Science B.V. All rights reserved. doi:10.1016/S0027-5107(03)00007-1