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RNA sequencing of an aneurysmal benign fibrous histiocytoma with the karyotype 46,XY,t(3;11)(p21;q13),del(6)(p23)[17]/46,XY[2] showed that the t(3;11) generated two fusion genes: LAMTOR1-PRKCD and NUMA1-SFMBT1. RT-PCR together with Sanger sequencing verified the presence of fusion transcripts from both fusion genes. In the LAMTOR1-PRKCD fusion, the part of the PRKCD gene coding for the catalytic domain of the serine/threonine kinase is under control of the LAMTOR1 promoter. In the NUMA1-SFMBT1 fusion, the part of the SFMBT1 gene coding for two of four malignant brain tumor domains and the sterile alpha motif domain is controlled by the NUMA1 promoter. The data support a neoplastic genesis of aneurysmal benign fibrous histiocytoma and indicate a pathogenetic role for LAMTOR1-PRKCD and NUMA1-SFMBT1.

Cancer-specific fusion genes are often caused by cytogenetically visible chromosomal rearrangements such as translocations, inversions, deletions or insertions, they can be the targets of molecular therapy, they play a key role in the accurate diagnosis and classification of neoplasms, and they are of prognostic impact. The identification of novel fusion genes in various neoplasms therefore not only has obvious research importance, but is also potentially of major clinical significance. The “traditional” methodology to detect them began with cytogenetic analysis to find the chromosomal rearrangement, followed by utilization of fluorescence in situ hybridization techniques to find the probe which spans the chromosomal breakpoint, and finally molecular cloning to localize the breakpoint more precisely and identify the genes fused by the chromosomal rearrangement. Although laborious, the above-mentioned sequential approach is robust and reliable and a number of fusion genes have been cloned by such means. Next generation sequencing (NGS), mainly RNA sequencing (RNA-Seq), has opened up new possibilities to detect fusion genes even when cytogenetic aberrations are cryptic or information about them is unknown. However, NGS suffers from the shortcoming of identifying as “fusion genes” also many technical, biological and, perhaps in particular, clinical “false positives,” thus making the assessment of which fusions are important and which are noise extremely difficult. The best way to overcome this risk of information overflow is, whenever reliable cytogenetic information is at hand, to compare karyotyping and sequencing data and concentrate exclusively on those suggested fusion genes that are found in chromosomal breakpoints. This article is part of a Directed Issue entitled: Rare Cancers.

While uterine leiomyomas are among the most common and best cytogenetically characterized solid tumors, leiomyomas at other sites are rare. Only two karyotypically abnormal leiomyomas in males have been reported to date, both of them with unspecific chromosome aberrations. We recently analyzed by G-banding a paratesticular leiomyoma, a tumor type not cytogenetically examined before, and found the pseudodiploid karyotype 46,XY,der(5)t(5;14)(q31;q24),der(14)t(12;14)(q15;q24). The leiomyoma cells demonstrated strong immunohistochemical nuclear expression of the HMGA2 protein, supporting a role of HMGA2 as the target gene in 12q14∼15 rearrangements. In uterine leiomyomas, the t(12;14)(q15;q24) is the most frequent translocation leading to overexpression of HMGA2, therefore it seems that a common pathogenetic pathway exists for benign smooth muscle tumors of both the female and male reproductive organs. The finding of this abnormality may help identify a scrotal tumor of uncertain biologic potential but with smooth muscle differentiation as benign.

To date, only 16 cytogenetically abnormal hemangiopericytomas (HP) have been reported. Despite this low number, some characteristic karyotypic features have already emerged: most HP are near-diploid and breakpoints in 12q13, 12q24, and 19q13 seem to be common, with t(12;19)(q13;q13) being a recurrent translocation. Here, we report the first case of a probably benign splenic HP with chromosomal abnormalities. The abnormal karyotype was 47,XX,t(5;22;11)(q31;q11;q13),+10. None of these abnormalities have previously been reported in HP, suggesting that the karyotypic pattern of splenic HP may differ from soft tissue HP.

Cytogenetic analysis of a transitional cell carcinoma (TCC) of the bladder, the tumor having developed 32 years after the patient received pelvic irradiation and interstitial radium implantation for an endometrial carcinoma, revealed the presence of 10 cytogenetically abnormal, unrelated clones. Although the tumor was poorly differentiated, all clones were pseudo- or near-diploid with rather simple balanced or unbalanced structural rearrangements or both. The chromosomes involved in structural changes more than once were chromosomes 8, 9, and 11, which were rearranged in three clones, and chromosomes 3 and 17, both rearranged in two clones. No previous TCC of the bladder with cytogenetically unrelated clones has been reported, nor has any such radiation-induced tumor with chromosomal abnormalities been described. The distinct karyotypic and clonal pattern of the case presented here is probably indicative of a carcinogenic field effect due to the previous pelvic irradiation. Postradiation bladder carcinomas thus seem to be distinct cytogenetically in addition to their known unique etiological and clinical features.

Inflammatory pseudotumors of the urinary bladder are rare, benign, nonepithelial tumors. Fewer than 30 have been reported, and no data are available on their karyotypic characteristics and/or the molecular mechanisms of pathogenesis. We performed short-term culturing and cytogenetic analysis of an inflammatory pseudotumor of the bladder, finding a der(20)t(12;20)(q13 approximately q15;q13) as the only cytogenetic aberration. The detection of a 12q13 approximately q15 rearrangement in the inflammatory pseudotumor indicates that this lesion is pathogenetically related to other benign mesenchymal tumors displaying, for example, lipogenic or leiomyomatous differentiation, something that is in sharp contrast to the karyotypic profile of epithelial tumors of the urinary bladder mucosa.