Schizophrenia (SCZ) is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits with heritability estimated at up to 80%1,2. We adopted two analytic approaches to determine the extent to which common genetic variation underlies risk of SCZ using genome-wide association study (GWAS) data from 3,322 European individuals with SCZ and 3,587 controls. First, we implicate the major histocompatibility complex (MHC). Second, we provide molecular genetic evidence for a substantial polygenic component to risk of SCZ involving thousands of common alleles of very small effect. We show that this component also contributes to risk of bipolar disorder (BPD), but not to multiple non-psychiatric diseases.

The study was undertaken with the aim to outline deletion patterns involving the long arm of chromosome 6, a common abnormality in lymphoproliferative disorders. Using a chromosome 6 specific tile path array, 60 samples from in total 49 cases with mantle cell lymphoma (MCL), de novo diffuse large B-cell lymphoma (DLBCL), transformed DLBCL as well as preceding follicular lymphoma (FL), and childhood acute lymphoblastic leukemia (ALL), were characterized. Twenty-six of the studied cases, representing all diagnoses, showed a 6q deletion among which 85% involved a 3 Mb region in 6q21. The minimal deleted interval in 6q21 encompasses the FOXO3A, PRDM1 and HACE1 candidate genes. The PRDM1 gene was found homozygously deleted in a case of DLBCL. Moreover, in two DLBCL cases, an overlapping homozygous deletion was identified in 6q23.3 - 24.1, encompassing the TNFAIP3 gene among others. Taken together, we refined the deletion pattern within the long arm of chromosome 6 in four different types of hematological malignances, suggesting the location of tumor suppressor genes involved in the tumor progression.

Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy, which is believed to originate from naive B-cells in the mantle zone of lymph nodes. Recently, a more diverse cellular origin has been implicated in MCL, since the disease was shown to consist of two subsets based on immunoglobulin heavy-chain variable (IGHV) gene analysis; a major subset with unmutated IGHV genes and a smaller subset (approximately 20 to 30%) displaying mutated IGHV genes. Presence of somatic hypermutation in the 'mutated' subset suggests either exposure to a germinal centre (GC) environment or that somatic hypermutation has been acquired in a non-GC context. Furthermore, a preferential IGHV gene utilization has been revealed in MCL, where IGHV3-21 and IGHV4-34 are the most predominant. MCLs with an IGHV3-21 usage almost exclusively share the same light chain (IGLV3-19) use and this subset is also related to a better prognosis. MCL cases utilising the IGHV3-21 gene display less chromosomal alterations than MCLs using other IGHV genes and in addition, gains in 15q and losses in 9p were not observed in any of these cases. These latter findings are in favour of the hypothesis that IGHV3-21(+) tumours may represent a distinct MCL subentity and that there is a possible role for antigens in MCL development. In this review, we will summarise these recent studies of IG gene rearrangements in MCL as well as molecular cytogenetic characteristics of this malignancy.

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A preferential use of one particular immunoglobulin variable heavy chain gene, V H 3-21, has recently been reported in mantle cell lymphoma, where almost all of these V H 3-21 þ mantle cell lymphomas showed usage of the same light chain V k gene (V k 3-19) and also had a tendency towards improved prognosis. These findings suggested that V H 3-21 þ mantle cell lymphomas constitute a distinct subgroup, possibly with antigen stimulation involved in disease pathogenesis. In this study, we applied the comparative genomic hybridization (CGH) method on 37 mantle cell lymphoma tumors in order to investigate if the V H 3-21 þ tumors are different at the genomic level. Interestingly, V H 3-21 þ mantle cell lymphomas (n ¼ 14) showed significantly fewer genomic aberrations (mean 2.4) compared to non-V H 3-21 mantle cell lymphomas (n ¼ 23) (mean 4.9). The chromosomal aberrations identified in our study were generally in accordance with previous CGH studies of mantle cell lymphoma; the most frequent aberration was complete or partial loss of chromosome 13, followed by recurrent losses within 6q, 9p, 9q and 11q and frequent gains in 3q, 7p, 8q and 15q. Deletions within 8p and 9p as well as gains in 7p and 15q were found exclusively in the non-V H 3-21-utilizing tumors. In summary, V H 3-21 þ mantle cell lymphomas demonstrated both a lower number and a different spectrum of genomic aberrations than mantle cell lymphoma in general, thus supporting the hypothesis that V H 3-21 þ mantle cell lymphomas constitute a new subgroup. The findings presented in this report may explain the tendency for a better clinical outcome for patients whose tumors utilize V H 3-21.