Tony L Ng

University of British Columbia | UBC · Department of Pathology and Laboratory Medicine

Objective: Laryngeal verrucous carcinoma (LVC) comprises 1% to 4% of all laryngeal tumors. Although controversial, surgery has been the mainstay of treatment, due to concern about anaplastic transformation with radiotherapy. We aimed to study LVC patients to identify treatment patterns for primary and recurrent diseases. Study design: Retrospect...

There is emerging evidence about the predictive role of homologous recombination deficiency (HRD), but this is less defined in gastrointestinal (GI) and thoracic malignancies. We reviewed whole genome (WGS) and transcriptomic (RNA-Seq) data from advanced GI and thoracic cancers in the Personalized OncoGenomics trial (NCT02155621) to evaluate HRD sc...

Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual’s cancer tha...

In this study, we evaluate the impact of whole genome and transcriptome analysis (WGTA) on predictive molecular profiling and histologic diagnosis in a cohort of advanced malignancies. WGTA was used to generate reports including molecular alterations and site/tissue of origin prediction. Two reviewers analyzed genomic reports, clinical history, and...

Nasopharyngeal carcinomas (NPC) are non-keratinizing squamous cell carcinomas of the nasopharynx associated with Epstein-Barr virus (EBV). When occurring outside of the nasopharynx, they are referred to as lymphoepithelioma-like carcinomas (LELCs) and present the same morphology as NPC. LELC have been described in other head and neck regions such a...

Purpose: Gene fusions are important oncogenic drivers and many are actionable. Whole-genome and transcriptome (WGS and RNA-seq, respectively) sequencing can discover novel clinically relevant fusions. Experimental design: Using WGS and RNA-seq, we reviewed the prevalence of fusions in a cohort of 570 patients with cancer, and compared prevalence...

PurposePrevious studies indicate that breast cancer molecular subtypes differ with respect to their dependency on autophagy, but our knowledge of the differential expression and prognostic significance of autophagy-related biomarkers in breast cancer is limited.Methods Immunohistochemistry (IHC) was performed on tissue microarrays from a large popu...

NanoString nCounter is a multiplex nucleic acid hybridization technology that enables reliable and reproducible assessment of the expression of up to 800 genes or 228 gene fusions in 12 samples in a single assay. The technique works well with a variety of starting materials from fresh or formalin-fixed tissues, cell lysates or biological fluid samp...

Sclerosing odontogenic carcinoma is a rare locally destructive neoplasm with many histologic mimics. Here the diagnostic challenges are presented of a case of sclerosing odontogenic carcinoma with variable histologic features, including unusual and unexpected negative immunostaining for CK19.

Case Report: Madura Foot

Case Report: Peripheral Amyloidoma of the Foot

PURPOSE This study investigated therapeutic potential of integrated genome and transcriptome profiling of metastatic sarcoma, a rare but extremely heterogeneous group of aggressive mesenchymal malignancies with few systemic therapeutic options. METHODS Forty-three adult patients with advanced or metastatic non-GI stromal tumor sarcomas of various...

Purpose Gene fusions involving neuregulin 1 (NRG1) have been noted in multiple cancer types and have potential therapeutic implications. Although varying results have been reported in other cancer types, the efficacy of the HER-family kinase inhibitor afatinib in the treatment of NRG1 fusion–positive pancreatic ductal adenocarcinoma is not fully un...

Eccrine porocarcinomas (EPs) are rare malignant tumours of the intraepidermic sweat gland duct and most often arise from benign eccrine poromas. Some recurrent somatic genomic events have been identified in these malignancies, but very little is known about the complexity of their molecular pathophysiology. We describe the whole genome and whole tr...

Thyroid-like follicular renal cell carcinoma (TLFRCC) is a rare cancer with few reports of metastatic disease. Little is known regarding genomic characteristics and therapeutic targets. We present the clinical, pathologic, genomic, and transcriptomic analyses of a case of a 27-yr-old male with TLFRCC who presented initially with bone metastases of...

Clinical detection of sequence and structural variants in known cancer genes points to viable treatment options for a minority of children with cancer.1 To increase the number of children who benefit from genomic profiling, gene expression information must be considered alongside mutations.2,3 Although high expression has been used to nominate drug...

We describe a novel gene fusion, EWSR1-CREM, identified in 3 cases of clear cell carcinoma (CCC) using anchored multiplex polymerase chain reaction, a next-generation sequencing-based technique. CCC is a low-grade salivary tumor recently characterized to have EWSR1-ATF1 fusions in the majority of cases. Three cases of malignant tumor presenting in...

Metastatic adenoid cystic carcinomas (ACCs) can cause significant morbidity and mortality. Because of their slow growth and relative rarity, there is limited evidence for systemic therapy regimens. Recently, molecular profiling studies have begun to reveal the genetic landscape of these poorly understood cancers, and new treatment possibilities are...

The incidence of HPV-positive oropharyngeal cancer (HPV+ OPC) is increasing, thus presenting new challenges for disease detection and management. Noninvasive methods involving brush biopsies of diseased tissues were recently reported as insufficient for tumor detection in HPV+ OPC patients, likely due to differences between the site of tumor initia...

Supplementary Table 1: it provides an overview of patient demographics for all individuals included in this study. Supplementary Table 2: it provides a description of the most important nuclear features as defined by our model.

Endometrial stromal sarcomas (ESSs) are mesenchymal uterine tumors characterized by recurrent genetic events, most commonly chromosomal rearrangements, that create oncogenic gene fusions. High-grade endometrial stromal sarcomas (HG-ESSs), as defined in the 2014 World Health Organization Classification, typically contain oncogenic YWHAE-NUTM2 fusion...

Ectopic thymoma in the neck is a rare phenomenon, with fewer than 20 cases reported worldwide. Evidence for management of ectopic thymoma comes from literature for mediastinal thymoma despite clinical features that distinguish the two. Here we present a case of a 31-year-old female with an asymptomatic neck mass who was found to have an ectopic cer...

The NanoString nCounter assay is a high-throughput hybridization technique using target-specific probes that can be customized to test for numerous fusion transcripts in a single assay utilizing RNA from formalin-fixed, paraffin-embedded material. We designed a NanoString assay targeting 174 unique fusion junctions in 25 sarcoma types. The study co...

BackgroundNRG1 fusion-positive lung cancers have emerged as potentially actionable events in lung cancer but clinical support is currently limited and no evidence of efficacy of this approach in cancers beyond lung has been shown.Patients and Methods Here we describe two patients with advanced cancers refractory to standard therapies. Patient 1 had...

Aims: Clear cell sarcoma of kidney (CCSK) is a rare paediatric renal malignant tumour. The majority of CCSKs have internal tandem duplications (ITD) of the BCOR gene while a minority has the YWHAE-NUTM2 gene fusion. A third 'double-negative' (DN) category comprises CCSKs with neither BCOR ITD nor YWHAE-NUTM2 fusion. The aim of this study was to ch...

Introduction: Autophagy, a lysosome-mediated degradation and recycling process, functions as an adaptive survival response during various stressful conditions including hypoxia and chemotherapy. The cysteine protease ATG4B, an important component of the autophagy pathway, is becoming a promising therapeutic target, but its value as a prognostic mar...

The most common benign salivary tumour is a pleomorphic adenoma. Transformation to malignancy, carcinoma ex pleomorphic adenoma (cxpa), occurs in 6% of cases. Management focuses on surgical resection and radiotherapy; however, rare cases require systemic management. We present the case of a 60-year-old woman with a cxpa of the left parotid gland wh...

Purpose: To evaluate the feasibility and to report the early outcomes of focal treatment of prostate cancer using low- dose-rate brachytherapy (LDR-PB). Material and methods: Seventeen patients were screened with multi-parametric magnetic resonance imaging (mpMRI), 14 of whom proceeded to receive trans-perineal template mapping biopsy (TTMB). Foca...

Introduction: We describe a woman with the known pathogenic germline variant CHEK2:c.1100delC and synchronous diagnoses of both pelvic genital type leiomyosarcoma and metastatic invasive ductal breast carcinoma. CHEK2 (checkpoint kinase 2) is a tumour suppressor gene encoding a serine/threonine-protein kinase (CHEK2) involved in double-strand DNA...

Inflammatory myofibroblastic tumor (IMT) can occur in a number of anatomic sites, including the uterus. Like its soft tissue counterpart, uterine IMT frequently expresses ALK and harbors ALK genetic rearrangements. The aim of this study is to fully characterize the genetic fusions that occur in uterine IMT. We studied 11 uterine IMTs with typical h...

Inflammatory myofibroblastic tumor (IMT) is a genetically heterogenous tumor of the viscera and soft tissues, with multiple molecular features having been demonstrated in this tumor type. About 50% of cases harbor an anaplastic lymphoma kinase (ALK) gene rearrangement, and recent studies have described novel fusions involving the ROS1 and PDGFRβ ge...

Aims: Endometrial stromal sarcomas (ESS) are divided into low-grade and high-grade subtypes with the latter exhibiting more aggressive clinical behavior. While histology and immunophenotype can aid in the diagnosis of these tumors, genetic studies can provide additional diagnostic insights as low-grade ESS frequently harbor fusions involving JAZF1...

Background: A patient suffering from metastatic colorectal cancer, treatment-related toxicity and resistance to standard chemotherapy and radiation was assessed as part of a personalized oncogenomics initiative to derive potential alternative therapeutic strategies. Patients and methods: Whole-genome and transcriptome sequencing was used to inte...

The etiology of deep dyspareunia in endometriosis is unclear. Our objective was to determine whether nerve bundle density in the cul-de-sac/uterosacrals (zone II) is associated with deep dyspareunia in women with endometriosis. We conducted a blinded retrospective immunohistochemistry study (n = 58) at a tertiary referral center (2011-2013). Patien...

Soft tissue myoepithelioma is a rare neoplasm composed of myoepithelial cells. We describe the cytologic features of a soft tissue myoepithelioma arising in the right lower chest wall in a 65-year-old woman. The fine-needle aspiration (FNA) smears showed round to oval, spindle, epithelioid, and plasmacytoid cells in the myxoid background. The nucle...

Mammary-analogue secretory carcinoma (MASC) is a recently described salivary gland tumour with a characteristic ETV6-NTRK3 translocation found in majority of the cases. MASC has also been reported three times as primary skin tumour; however, none of these cases showed the translocation. We recently encountered a case of an asymptomatic cutaneous no...

Background Breast cancer is a complex disease with clinical, pathological, and molecular heterogeneity. Recent studies have identified several subtypes of breast cancers driven by specific molecular pathways that can be inhibited by targeted drugs. We studied the feasibility of using molecular data from whole genome and transcriptome sequencing of...

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Perivascular epithelioid cell tumours (pecomas) are rare mesenchymal tumours that are characterized by perivascular epithelioid cell differentiation and immunoreactivity to myogenic and melanocytic markers. These tumours can be classified as benign, uncertain malignant potential, or malignant. Because of the rarity of pecomas, their cause and clini...

Under cell stress, global protein synthesis is inhibited to preserve energy. One mechanism is to sequester and silence mRNAs in ribonucleoprotein complexes known as stress granules (SGs), which contain translationally silent mRNAs, preinitiation factors, and RNA-binding proteins. Y-box binding protein 1 (YB-1) localizes to SGs, but its role in SG b...

We describe how the combination of imaging and histologic findings was essential in establishing a preoperative diagnosis of an extremely rare malignant granular cell tumor (GrCT) occurring in the lower extremity of a 17-year-old man. Magnetic resonance imaging (MRI) demonstrated a large infiltrative tumor of heterogeneous intermediate signal inten...

Rare cancer types are not only understudied, but are typically represented by formalin-fixed paraffin-embedded (FFPE) (rather than freshly-frozen) specimens that are suboptimal for genomic analysis. Ameloblastoma is one such rare tumor type, thought to arise from ameloblasts, the cells that deposit enamel during tooth development. Though typically...

Aim: Tumour heterogeneity poses a significant challenge to the success of treatment; tumours with similar histological features may have substantially different biological drivers. This analysis is part of a study in which we use whole genome and transcriptome sequencing to aid in therapeutic decision-making in patients (pts) with advanced cancers....

Here we report the discovery of oncogenic mutations in the Hedgehog and mitogen-activated protein kinase (MAPK) pathways in over 80% of ameloblastomas, locally destructive odontogenic tumors of the jaw, by genomic analysis of archival material. Mutations in SMO (encoding Smoothened, SMO) are common in ameloblastomas of the maxilla, whereas BRAF mut...

Suppression of anoikis after detachment of cancer cells from the extracellular matrix is a key step during metastasis. Here we show that, after detachment, mouse embryonic fibroblasts (MEFs) transformed by K-Ras(V12) or ETV6-NTRK3 (EN) activate a transcriptional response overrepresented by genes related to bioenergetic stress and the AMP-activated...

The insulin-like growth factor-1 receptor (IGF1R) is emerging as a promising therapeutic target in human cancers. In the high-risk childhood sarcomas Ewing family tumor and rhabdomyosarcoma, IGF1R-blocking antibodies show impressive antitumor activity in some but not all patients, and acquired resistance is observed. Because tumor IGF1R mutations a...

Learning Objectives After completing this course, the reader will be able to: Explain the importance of resistance to anoikis in the development of metastases.Describe the mechanisms of anoikis resistance in EFTs and osteosarcoma and their potential use in development of new therapies. CME This article is available for continuing medical education...

Hyperproliferation induced by various oncogenic proteins, including activated Ras, is the most prominent and well characterized feature of cancerous cells. This property has been exploited in the development of the most successful anti-cancer treatments to target rapidly dividing cells. Here we argue that hyperproliferation may in fact be detriment...

Multiple members of the let-7 family of miRNAs are often repressed in human cancers, thereby promoting oncogenesis by derepressing targets such as HMGA2, K-Ras and c-Myc. However, the mechanism by which let-7 miRNAs are coordinately repressed is unclear. The RNA-binding proteins LIN28 and LIN28B block let-7 precursors from being processed to mature...