Consistent involvement of chromosome 13 in angiolipoma

Background/Aim: Angiolipoma is a rare benign soft tissue tumor composed of mature adipocytes and blood vessels. Genetic information on angiolipomas is scarce. With the single exception of one tumor which carried a t(X;2)(p22;p12), all angiolipomas hitherto investigated cytogenetically had normal karyotypes. Materials and Methods: G-banding chromosome analysis was performed on three short-term cultured angiolipomas. Fluorescence in situ hybridization (FISH) analysis using a commercially available RB1 deletion probe was also done. Results: All three angiolipomas had abnormal karyotypes with loss or structural rearrangement of chromosome 13. The first tumor had the karyotype 46,XY,-6,del(13)(q14),+mar[cp5], the second had 44~45,XY,t(1;10;15)(p21~22;q24;q24),-13[cp5], and the third karyotype was 43,XX,t(13;22;17) (q12;q13; q22~23)[14]. FISH analysis showed heterozygous and homozygous deletion of the RB1 probe in case 2 and 3, respectively. FISH analysis failed in case 1. Conclusion: Chromosome 13 was consistently involved in all three angiolipomas

Chronic expanding hematoma with a t(11;19)(q13;q13) chromosomal translocation

Background/Aim: Chronic expanding hematoma is defined as a hematoma that gradually expands over 1 month or longer, is without neoplastic features on histological sections, and does not occur in the setting of coagulopathy. The pathogenetic mechanism behind its development is unknown, nor is anything known about its genetic features. Case Report: A 49-year-old man noted a tender lump close to the right femoral trochanter. Examination of a core needle biopsy showed a fibrous capsule with fibrinoid material on one side. The patient underwent surgery with removal of a cystic, encapsulated structure with central bleeding and proliferating vessels in the fibrous capsule. The reactive fibroblasts were without any sign of atypia. Genetic analyses were performed on this chronic expanding hematoma. Results: G-Banding analysis of short-term cultured cells from the chronic expanding hematoma yielded a karyotype with a single clonal chromosome abnormality: 46,XY,t(11;19)(q13;q13)[8]/46,XY[10]. RNA sequencing and examination of the sequencing data using five different programs did not identify fusion genes related to the translocation. Conclusion: The acquired translocation t(11;19)(q13;q13) suggested that chronic expanding hematoma is a neoplastic lesion. Since the translocation did not lead to any fusion genes, one can speculate that it causes deregulation of gene expression

Fusion of the COL4A5 gene with NR2F2-AS1 in a hemangioma carrying a t(X;15)(q22;q26) chromosomal translocation

Background/Aim: Hemangiomas are benign neoplastic proliferations of blood vessels. Cytogenetic information on hemangiomas is limited to four tumors with abnormal karyotypes. We report here a solitary chromosomal translocation and its molecular consequence in a hemangioma. Materials and Methods: A cavernous hemangioma was extirpated from the foot of a 62 years old man and genetically studied with cytogenetic and molecular genetic methodologies. Results: G-Banding analysis of short-term cultured tumor cells yielded the karyotype 46,Y,t(X;15)(q22;q26)[4]/46,XY[12]. RNA sequencing detected fusion of the collagen type IV alpha 5 chain gene (COL4A5 on Xq22.3) with intronic sequences of nuclear receptor subfamily 2 group F member 2 antisense RNA 1 (NR2F2-AS1 on 15q26.2) resulting in a putative COL4A5 truncated protein. The fusion was verified by RT-PCR together with Sanger sequencing and FISH analyses. Conclusion: The involvement of COL4A5 indicates that some hemangiomas have pathogenetic similarities with other benign tumors such as leiomyomas and subungual exostosis

NDRG1-PLAG1 and TRPS1-PLAG1 fusion genes in chondroid syringoma

Background/Aim: Chondroid syringoma is a rare benign tumor emanating from sweat glands. Although rearrangements of the pleomorphic adenoma gene 1 (PLAG1) have been reported in such tumors, information on PLAG1 fusion genes is very limited. Materials and Methods: Cytogenetic, fluorescence in situ hybridization, RNA sequencing, array comparative genomic hybridization, reverse transcription polymerase chain reaction, and Sanger sequencing analyses were performed on two chondroid syringoma cases. Results: Both tumors had structural rearrangements of chromosome 8. An NDRG1-PLAG1 transcript was found in the first tumor in which exon 3 of PLAG1 was fused with exon 1 of NDRG1. A TRPS1-PLAG1 chimeric transcript was detected in the second chondroid syringoma in which exon 2 or exon 3 of PLAG1 was fused with exon 1 of TRPS1. Conclusion: The NDRG1-PLAG1 and TRPS1-PLAG1 resemble other PLAG1 fusion genes inasmuch as the expression of PLAG1 comes under the control of the NDRG1 or TRPS1 promoter

Fusion of the Lumican (LUM) Gene with the Ubiquitin Specific Peptidase 6 (USP6) Gene in an Aneurysmal Bone Cyst Carrying a t(12;17)(q21;p13) Chromosome Translocation

Background/Aim: Aneurysmal bone cyst is a benign bone lesion with a strong tendency to recur. The rearrangement of chromosome band 17p13/USP6 gene is now considered a characteristic genetic feature of aneurysmal bone cyst, with t(16;17)(q22;p13)/CDH11-USP6 as the most frequent chromosomal aberration/fusion gene. We report a novel variant translocation leading to a new fusion gene in an aneurysmal bone cyst. Materials and Methods: Genetic analyses were performed on an aneurysmal bone cyst found in the tibia of a child. Results: G-banding chromosome analysis yielded the karyotype 46,XX,t(12;17)(q21;p13)[5]/46,XX[2]. FISH analysis with a USP6 break-apart probe showed rearrangement of USP6. RNA sequencing detected LUM-USP6 and USP6-LUM fusion transcripts which were subsequently verified by RT-PCR/Sanger sequencing. The two genes exchanged 5’- non-coding exons. Thus, promoter swapping between USP6 and LUM had taken place. Conclusion: We report a novel t(12;17)(q21;p13) chromosome translocation which gave rise to a LUM-USP6 fusion in an aneurysmal bone cyst

FOS-ANKH and FOS-RUNX2 fusion genes in osteoblastoma

Background/Aim: Osteoblastoma is a rare benign tumor of the bones in which recurrent rearrangements of FOS have been found. Our aim was to investigate two osteoblastomas for possible genetic aberrations. Materials and Methods: Cytogenetic, RNA sequencing, and molecular analyses were performed. Results: A FOS-ANKH transcript was found in the first tumor, whereas a FOS-RUNX2 was detected in the second. Exon 4 of FOS fused with sequences either from intron 1 of ANKH or intron 5 of RUNX2. The fusion events introduced a stop codon and removed sequences involved in the regulation of FOS. Conclusion: Rearrangements and fusions of FOS show similarities with those of HMGA2 (a feature of leiomyomas and lipomas) and CSF1 (tenosynovial giant cell tumors). The replacement of a 3’-untranslated region, controlling the gene's expression, by a new sequence is thus a common pathogenetic theme shared by FOS, HMGA2, and CSF1 in many benign connective tissue tumors

Fusion of the COL1A1 and Fyn genes in epithelioid osteoblastoma

Background/Aim: Epithelioid osteoblastoma is a rare benign tumor of the bone. Its pathogenesis is unknown and little is known regarding its genetic features. Materials and Methods: Cytogenetic, RNA sequencing, reverse transcription polymerase chain reaction (RT-PCR), genomic PCR, and Sanger sequencing analyses were performed on an epithelioid osteoblastoma. Results: G-banding analysis of short-term cultured tumor cells yielded a normal male karyotype in all examined metaphases. RNA sequencing detected a fusion of COL1A1 from 17q21 with FYN from 6q21. Both RT-PCR and genomic PCR together with Sanger sequencing verified the presence of a COL1A1-FYN fusion gene. In the COL1A1-FYN chimeric transcript, exon 43 of COL1A1 was fused to exon 2 of FYN. The genomic junction occurred in introns 43 and 1 of COL1A1 and FYN, respectively. Conclusion: A COL1A1-FYN fusion gene was found in an epithelioid osteoblastoma resulting in deregulation of FYN. Whether COL1A1-FYN represents a consistent genetic feature of epithelioid osteoblastomas, remains to be seen

Recurrent fusion of the GRB2 associated binding protein 1 (GAB1) gene with ABL proto-oncogene 1 (ABL1) in benign pediatric soft tissue tumors

Background/Aim: Fusions of the ABL proto-oncogene 1 gene (ABL1 in 9q34) are common in leukemias but rare in solid tumors. The most notable is the t(9;22)(q34;q11)/BCR-ABL1 coding for a chimeric tyrosine kinase. We herein report an ABL1-fusion in a pediatric tumor. Materials and Methods: G-banding, fluorescence in situ hybridization, reverse transcription polymerase chain reaction and Sanger sequencing were performed on a soft tissue perineurioma found in the left musculus erector spinae of a child. Results: A der(4)t(4;9)(q31;q34) and a fusion of the GRB2 associated binding protein 1 (GAB1 in 4q31) gene with ABL1 were found. A literature search revealed 3 more cases with similar genetic and clinicopathological characteristics: a soft tissue perineurioma with t(2;9;4)(p23;q34;q31) and ABL1 rearrangement, a soft tissue angiofibroma with a GAB1-ABL1 chimeric gene, and a solitary fibrous tumor carrying a der(4)t(4;9)(q31.1;q34). Conclusion: GAB1-ABL1 is a recurrent fusion gene in benign pediatric tumors

Cytogenetics of spindle cell/pleomorphic lipomas: Karyotyping and fish analysis of 31 tumors

Background: Spindle cell/pleomorphic lipomas are benign tumors. Here, we present our cytogenetic data on 31 such tumors. Materials and Methods: G-banding chromosome analysis and (in selected cases) fluorescence in situ hybridization (FISH) using probes for FOXO1, RB1, and HMGA2 were performed. Results: Rearrangements of chromosome 13 were found in 58% of tumors. Chromosomes 6, 1, 12, and 11 were also involved in 42%, 26%, 26%, and 23% of tumors, respectively. FISH analysis showed heterozygous deletion of RB1 in seven samples with chromosome 13 aberrations. In four of them, FOXO1 was also deleted. In two tumors with 12q15 rearrangements, FISH confirmed that HMGA2 was targeted. Conclusion: Structural rearrangements of 13q or losses of an entire chromosome 13 are the most common cytogenetic aberrations in spindle cell/pleomorphic lipomas. However, cytogenetic variation exists similarly to what is found in other lipomas, suggesting that various pathways may be responsible for tumorigenesis