A Unique Case Report of Infant-Type Hemispheric Glioma (Gliosarcoma Subtype) with TPR-NTRK1 Fusion Treated with Larotrectinib

Herein, we present a rare case of a nine-month-old boy diagnosed with infant-type hemispheric glioma (gliosarcoma subtype) at the left frontal lobe. Following subtotal resection, the patient started chemotherapy with the BABY POG protocol. We describe the clinical diagnosis, histological characteristics, radiological features, molecular aspects, and management of this tumor. A comprehensive molecular analysis on the tumor tissue showed a <i>TPR-NTRK1</i> gene fusion. The patient was treated with a TRK inhibitor, larotrectinib, and exhibited a stable disease with residual lesion following 8 months of target therapy. The present study is the first report of an infantile gliosarcoma harboring <i>NTRK1</i> rearrangement treated with larotrectinib.

Development of an RNA sequencing panel to detect gene fusions in thyroid cancer

In addition to mutations and copy number alterations, gene fusions are commonly identified in cancers. In thyroid cancer, fusions of important cancer-related genes have been commonly reported; however, extant panels do not cover all clinically important gene fusions. In this study, we aimed to develop a custom RNA-based sequencing panel to identify the key fusions in thyroid cancer. Our ThyChase panel was designed to detect 87 types of gene fusion. As quality control of RNA sequencing, five housekeeping genes were included in this panel. When we applied this panel for the analysis of fusions containing reference RNA (HD796), three expected fusions (EML4-ALK, CCDC6-RET, and TPM3-NTRK1) were successfully identified. We confirmed the fusion breakpoint sequences of the three fusions from HD796 by Sanger sequencing. Regarding the limit of detection, this panel could detect the target fusions from a tumor sample containing a 1% fusion-positive tumor cellular fraction. Taken together, our ThyChase panel would be useful to identify gene fusions in the clinical field.

RNA-driven JAZF1-SUZ12 gene fusion in human endometrial stromal cells

Oncogenic fusion genes as the result of chromosomal rearrangements are important for understanding genome instability in cancer cells and developing useful cancer therapies. To date, the mechanisms that create such oncogenic fusion genes are poorly understood. Previously we reported an unappreciated RNA-driven mechanism in human prostate cells in which the expression of chimeric RNA induces specified gene fusions in a sequence-dependent manner. One fundamental question yet to be addressed is whether such RNA-driven gene fusion mechanism is generalizable, or rather, a special case restricted to prostate cells. In this report, we demonstrated that the expression of designed chimeric RNAs in human endometrial stromal cells leads to the formation of JAZF1-SUZ12, a cancer fusion gene commonly found in low-grade endometrial stromal sarcomas. The process is specified by the sequence of chimeric RNA involved and inhibited by estrogen or progesterone. Furthermore, it is the antisense rather than sense chimeric RNAs that effectively drive JAZF1-SUZ12 gene fusion. The induced fusion gene is validated both at the RNA and the genomic DNA level. The ability of designed chimeric RNAs to drive and recapitulate the formation of JAZF1-SUZ12 gene fusion in endometrial cells represents another independent case of RNA-driven gene fusion, suggesting that RNA-driven genomic recombination is a permissible mechanism in mammalian cells. The results could have fundamental implications in the role of RNA in genome stability, and provide important insight in early disease mechanisms related to the formation of cancer fusion genes.

Ung thư biểu mô tế bào thận có đột biến TFE3/Xp11.2 báo cáo một trường hợp ở trẻ em và đối chiếu y văn

TÓM TẮT Ung thư biểu mô tế bào thận (UTBM) - Renal cell carcinoma là khối u ác tính hiếm gặp, chỉ chiếm 2 - 6% các khối u thận ác tính ở trẻ em. UTBM tế bào thận có đột biến TFE3 trên nhiễm sắc thể Xp11.2 (TFE3/ Xp11.2) là một dưới nhóm của UTBM tế bào thận, thường có tiên lượng nặng hơn các nhóm khác của UTBM tế bào thận. Chúng tôi thông báo một trẻ 10 tuổi vào viện vì đau bụng và phát hiện khối u thận trái. Sau khi phẫu thuật cắt u được làm xét nghiệm mô bệnh học, nhuộm hóa mô miễn dịch TFE3(+), CD10(+), CK7(-) chẩn đoán: UTBM tế bào thận có đột biến TFE3/Xp11.2. Bệnh nhân ổn định, ra viện sau 2 tuần. Tái khám sau hai tháng không phát hiện u tái phát hay di căn. ABSTRACT RENAL CELL CARCINOMA ASSOCIATED WITH XP11.2 TRANSLOCATION FACTORE3 GENE FUSION: A CHILD CASE REPORT AND LITERATURE REVIEW Renal cell carcinoma is a rare malignancy, accounting for only 2 - 6% of renal malignancies in children. Renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion is a subgroup of renal cell carcinoma, often with a more severe prognosis than other groups of renal cell carcinoma. We report on a 10 - year - old child was admitted to the hospital because of abdominal painand a left kidney tumor. After tumor resection, histopathological examination, immunohistochemical staining was positive for TFE3, CD10, negative for CK7, diagnosis renal cell carcinoma associated with Xp11.2 translocation factor E3 gene fusion. Two weeks after surgery, the patient was stable and discharged from the hospital. Re - examination after two months did not detect tumor recurrence or metastasis. Key word: Renal cell carcinoma, TFE3, Xp11.2 translocation.