Abstract Introduction: Reinke’s Edema (RE) is a laryngeal lesion related to excessive tobacco smoking, voice overuse, and laryngopharyngeal reflux. Although the risk of malignancy has been considered low in literature, RE is classified among precancerous lesions. Objectives: We investigated DNA Copy Number Alterations (CNAs) in specimens of RE and its potential association with malignant progression. Methods: We used array-based comparative genomic hybridization (aCGH, Agilent 4 × 180 K platform) to study eight RE cases. All patients were heavy tobacco users for at least 30 years, and none of them progressed to cancer in the follow-up (>8 years). Two RE presented mild dysplasia, one moderate dysplasia, and no histological alterations were found in the remaining five cases. CNAs were compared with the Database of Genomic Variants (DGV) and genes mapped on altered regions had their functions annotated. Results: Six of eight patients showed different rare copy number alterations on chromosomes 2q37.3, 4q13.1, 4q13.3, 7q11.22, 10p14, and 13q34. A gain of the whole chromosome 8 were detected in one case. Of interest, four of eight RE cases showed copy number imbalances involving genes previously described in several tumor types (RASA3, COL6A3, LINC00707, LINP1, SMR3A, and SMR3B). Conclusion: The genomic imbalances herein found in RE have the potential to contribute to the phenotype but with limited or no risk of cancer. A long-term follow-up in a large series of patients could clarify the mechanisms involved in the malignant progression of RE. Level of evidence: 4. Introduction Reinkes Reinke s (RE smoking overuse reflux literature lesions Objectives (CNAs Methods arraybased array based aCGH, aCGH (aCGH 18 platform 3 years followup follow up >8 (> years. . years) dysplasia DGV (DGV annotated Results 2q373 q 2q37 2q37.3 4q131 4q13 1 4q13.1 4q133 4q13.3 7q1122 7q11 22 7q11.22 10p14 p 13q34 case interest RASA3, RASA3 RASA (RASA3 COL6A3 COLA COL LINC00707 LINC LINP1 LINP SMR3A SMRA SMR SMR3B. SMR3B SMRB B SMR3B) Conclusion longterm long term evidence > ( 2q3 2q37. 4q1 4q13. 7q112 7q1 2 7q11.2 10p1 13q3 (RASA COL6A LINC0070 2q 4q 7q 7q11. 10p 13q LINC007 LINC00 LINC0

A síndrome de Bannayan-Riley-Ruvalcaba é afecção rara, causada por mutações no gene PTEN. Apresenta associação de múltiplos lipomas, macrocefalia, hemangiomas, polipose hamartomatosa intestinal, atraso do desenvolvimento e máculas salpicadas na genitália masculina. Relatamos o caso de um menino de nove meses com lesões tumorais de crescimento rápido e progressivo em três meses de evolução, macrocefalia e lentigos no pênis. Exames de imagem demonstraram extensa lipomatose com invasão da musculatura paraespinhal, alargamento do canal vertebral e compressão medular. Depois da excisão cirúrgica da massa, o anatomopatológico foi compatível com lipoma. A análise do cariótipo em cultura de adipócitos demonstrou mutação do PTEN. Apresentamos este caso por sua exuberância e raridade.

Bannayan-Riley-Ruvalcaba Syndrome is a rare condition caused by mutations in the PTEN gene. It displays association of multiple lipomas, macrocephaly, hemangiomas, hamartomatous intestinal polyposis, developmental delay and speckled pigmented maculae on the male genitalia. We report the case of a nine-month-old boy who had fast growing and progressive tumors for three months, macrocephaly and lentigines on the penis. Imaging tests showed extensive lipomatosis with invasion of paraspinal muscles, enlargement of the spinal canal and spinal cord compression; after surgical excision of the mass, the pathology was consistent with lipoma. Adipocyte culture karyotype demonstrated PTEN mutation. We present this case for its rarity and exuberance.

We applied a combination of comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH), to characterize the genetic aberrations in three osteosarcomas (OS) and one Ewing's sarcoma. CGH identified recurrent chromosomal losses at 10p14-pter and gains at 8q22.3-24.1 in OS. Interphase FISH allowed to confirm 8q gain in two cases. A high amplification level of 11q12-qter was detected in one OS. The Ewing's sarcoma showed gain at 1p32-36.1 as the sole chromosome alteration. These studies demonstrate the value of molecular cytogenetic methods in the characterization of recurrent genomic alterations in bone tumor tissue.

Foi realizada análise cromossômica em lesões de três pacientes que, de acordo com critérios histopatológicos clássicos, não continham células tumorais. Além de células normais, nós identificamos cariótipos anormais com alterações cromossômicas clonais numéricas e estruturais em pelo menos duas culturas primárias originadas independentemente de cada lesão. Nossos dados sugerem que aberrações cromossômicas podem existir in vivo em lesões não neoplásicas. Outras anormalidades podem ser devidas a instabilidade genética manifestada apenas in vitro (artefatos de cultura) ou podem já estar presentes no tecido cerebral, refletindo danos cromossômicos prévios (como resultado de exposição a clastógenos químicos ou ambientais).

Chromosome analysis was made of brain lesions from three patients which, according to classical histopathological criteria, did not contain tumor cells. In addition to normal cells, we identified abnormal karyotypes with clonal numerical and structural chromosome alterations in at least two independently originated primary cultures from each lesion. Our data suggest that chromosomal aberrations can exist in vivo in non-neoplastic lesions. Other abnormalities may be due to genetic instability manifested only in vitro (culture artifacts) or may already have been present in brain tissue, reflecting previous chromosome damage (as a result of exposure to chemical treatment or enviromental clastogens).