Genomic alterations in human epidermal growth factor receptor 2 (HER2/ERBB2) in head and neck squamous cell carcinoma.

BACKGROUND: Despite recent advances, survival outcomes for those with metastatic or recurrent head and neck squamous cell carcinoma (HNSCC) have remained poor. Novel approaches should be investigated to improve outcomes. METHODS: A retrospective chart review was performed of a patient who presented with a TNM classification III HNSCC of the oropharynx, positive for human papillomavirus (HPV) who had a complete response to a human epidermal growth factor receptor 2 (HER2)-targeted therapy. Amplification rates of HER2 in the HNSCC Cancer Genome Atlas Network (TCGA) dataset and the FoundationOne genomic profiling dataset were evaluated. RESULTS: Comprehensive genomic profiling of the tumor obtained from the dermal metastasis identified amplification of HER2. Data from TCGA and FoundationOne showed that the frequency of HER2 alteration was not observed to vary significantly with HPV tumor status. CONCLUSION: This case demonstrates the application of genomic profiling to guide treatments in a patient with HNSCC with advanced metastatic disease refractory to standard of care therapies. © 2016 Wiley Periodicals, Inc. Head Neck 39: E15-E19, 2017.

Genomic Profiling of a Large Set of Diverse Pediatric Cancers Identifies Known and Novel Mutations across Tumor Spectra.

Pediatric cancers are generally characterized by low mutational burden and few recurrently mutated genes. Recent studies suggest that genomic alterations may help guide treatment decisions and clinical trial selection. Here, we describe genomic profiles from 1,215 pediatric tumors representing sarcomas, extracranial embryonal tumors, brain tumors, hematologic malignancies, carcinomas, and gonadal tumors. Comparable published datasets identified similar frequencies of clinically relevant alterations, validating this dataset as biologically relevant. We identified novel ALK fusions in a neuroblastoma (BEND5-ALK) and an astrocytoma (PPP1CB-ALK), novel BRAF fusions in an astrocytoma (BCAS1-BRAF) and a ganglioglioma (TMEM106B-BRAF), and a novel PAX3-GLI2 fusion in a rhabdomyosarcoma. Previously characterized ALK, NTRK1, and PAX3 fusions were observed in unexpected malignancies, challenging the "disease-specific" alterations paradigm. Finally, we identified recurrent variants of unknown significance in MLL3 and PRSS1 predicted to have functional impact. Data from these 1,215 tumors are publicly available for discovery and validation. Cancer Res; 77(2); 509-19. ©2017 AACR.

Durable clinical benefit to trastuzumab and chemotherapy in a patient with metastatic colon adenocarcinoma harboring ERBB2 amplification.

Somatic ERBB2 amplification or activating mutations occur in approximately 2-5% of metastatic colorectal adenocarcinomas and are presumed to be oncogenic drivers, but limited evidence exists to suggest these lesions are sensitive to targeted monotherapy in patients. Here we present the case of a patient with advanced CRC with pulmonary metastases, who had progressed on both standard of care cytotoxic chemotherapy and anti-EGFR targeted therapy. Comprehensive genomic profiling (FoundationOne(®)) identified amplification of ERBB2 and a TP53 mutation in the metastatic lesion. Treatment with trastuzumab with a chemotherapy backbone elicited stable disease/minor response in the patient over a one year course of therapy, reducing tumor burden and significantly improving quality of life. This report demonstrates the application of personalized targeted therapy guided by comprehensive genomic profiling in metastatic colorectal adenocarcinoma.