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Identification of a therapeutic target using molecular sequencing for treatment of recurrent uterine serous adenocarcinoma.

ABSTRACT: Uterine serous adenocarcinoma is a rare but highly malignant form of endometrial cancer, comprising over 50% of recurrences and deaths from endometrial cancer. We report a case of a 68-year old woman with recurrent uterine serous adenocarcinoma who underwent molecular testing and genetic sequencing of her tumor. She was found to have focal amplification of ERBB2 confirmed by amplification and overexpression of HER2/neu via fluorescence in situ hybridization and immunohistochemistry. Given the identification of this potential target and progression of disease, trastuzumab was added to the patient's chemotherapy regimen with ultimate complete response.

SUBMITTER: Musselman K

PROVIDER: S-EPMC6411491 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Identification of a therapeutic target using molecular sequencing for treatment of recurrent uterine serous adenocarcinoma.

Musselman Kelsey K Glynn Shannon S Mosquera Juan Miguel JM Elemento Olivier O Sboner Andrea A Beltran Himisha H Holcomb Kevin K

Gynecologic oncology reports 20190221

Uterine serous adenocarcinoma is a rare but highly malignant form of endometrial cancer, comprising over 50% of recurrences and deaths from endometrial cancer. We report a case of a 68-year old woman with recurrent uterine serous adenocarcinoma who underwent molecular testing and genetic sequencing of her tumor. She was found to have focal amplification of ERBB2 confirmed by amplification and overexpression of HER2/<i>neu via</i> fluorescence <i>in situ</i> hybridization and immunohistochemistry ...[more]

PMID: 30906838

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Project description:Background:Pancreatic ductal adenocarcinoma (PDAC) is an aggressive gastrointestinal cancer characterized by an extremely low survival rate because of early metastasis. Identifying satisfactory therapeutic targets associated with metastasis is crucial to improve the treatment effect of PDAC. Materials and methods:In this research, we used stable isotope labeling by amino acids in cell culture, 1-dodecyl-3-methylimidazolium chloride-assisted sample preparation method preparing protein sample and nano-reversed-phase liquid chromatography-mass spectrometry/mass spectrometry analysis to perform the comparative proteomics of two homologous hamster pancreatic cancer cell lines that are different in metastatic ability: PC-1.0 (highly metastatic) and PC-1 (weakly metastatic). Verifications are through immunohistochemistry on clinical human PDAC pathologic tissues as well as by Western blot of human pancreatic cancer cell lines. siRNA silencing methods were used to study the effect of molecules on invasion and metastasis of pancreatic cancer cell lines. Results:Bioinformatic analysis indicated that a total of 141 differentially expressed proteins (82 upregulated and 59 downregulated in PC-1.0 cells) were identified showing obviously differential expression (>1.5-fold change). These differentially expressed proteins were involved in a number of different biologic functions, metabolic pathways, and pathophysiologic processes. Phosphoglycerate mutase 1 (PGAM1) and HSPE1 are the top two upregulated proteins, and PDIA3 and CALR are the top two downregulated proteins in PC-1.0 cells compared to PC-1 cells. PGAM1 and HSPE1 showed higher expressions in PDAC tissue with clinical metastasis and highly metastatic pancreatic cancer cell lines PC-1.0 and Aspc-1. PDIA3 and CALR showed higher expressions in weakly metastatic pancreatic cancer cell lines PC-1 and Capan-2. The Western blot results were consistent with the MS quantification data. Silencing PGAM1 was found to decrease the migration and invasion of pancreatic cancer cell lines with statistical significance, especially in highly metastatic PC-1.0 and Aspc-1 cell lines. Conclusion:These data indicated that PGAM1 may be a potential therapeutic target for PDAC metastasis.

Dataset Information

Identification of a therapeutic target using molecular sequencing for treatment of recurrent uterine serous adenocarcinoma.

Publications

Identification of a therapeutic target using molecular sequencing for treatment of recurrent uterine serous adenocarcinoma.

Similar Datasets

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