Kaitlyn Zenner

University of Washington Seattle | UW · Department of Otolaryngology/Head and Neck Surgery

Objectives Patients born with bilateral head and neck lymphatic malformations (BHNLMs) often require multiple invasive treatments, including tracheostomy. We hypothesized that primary targeted medical therapy (pTMT) with diagnostic needle aspiration reduces the need for invasive therapy such as surgical resection and/or sclerotherapy. Methods Retr...

Purpose PIK3CA-related overgrowth spectrum (PROS) conditions of the head and neck are treatment challenges. Traditionally, these conditions require multiple invasive interventions, with incomplete malformation removal, disfigurement, and possible dysfunction. Use of the PI3K inhibitor alpelisib, previously shown to be effective in PROS, has not bee...

Somatic activating variants in PIK3CA, the gene that encodes the p110α catalytic subunit of PI3K, have been previously detected in ∼80% of lymphatic malformations (LM).1; 2 We report the presence of somatic activating variants in BRAF in individuals with LM that do not possess pathogenic PIK3CA variants. The BRAF substitution p.Val600Glu (c.1799T>A...

Disorganized morphogenesis of arteries, veins, capillaries, and lymphatic vessels results in vascular malformations. Most individuals with isolated vascular malformations have postzygotic (mosaic), activating pathogenic variants in a handful of oncogenes within the PI3K–RAS–MAPK pathway (Padia et al., Laryngoscope Investig Otolaryngol 4: 170–173 [2...

Somatic activating variants in PIK3CA , the gene that encodes the p110α catalytic subunit of PI3K, have been previously detected in ~80% of lymphatic malformations (LM). We report the presence of somatic activating variants in BRAF in individuals with PIK3CA -negative LM. The BRAF substitution p.Val600Glu (c.1799T>A), one of the most common driver...

Objectives Head and neck lymphatic malformations (HNLM) are caused by gain-of-function somatic mutations in PIK3CA. Acetylsalicylic acid (ASA/aspirin) is thought to limit growth in PIK3CA-mutated neoplasms through PI3K pathway suppression. We sought to determine if ASA could be beneficial for HNLM. Methods Retrospective case series of patients (0–...

Purpose: Vascular malformations (VM) are primarily caused by somatic activating pathogenic variants in oncogenes. Targeted pharmacotherapies are emerging but require molecular diagnosis. Since variants are currently only detected in malformation tissue, patients may be ineligible for clinical trials prior to surgery. We hypothesized that cell-free...

Lymphatic malformations (LMs) are congenital, non-neoplastic vascular malformations associated with post-zygotic activating PIK3CA mutations. The mutation spectrum within LMs is narrow, with the majority having one of three "hotspot" mutations. Despite this relative genetic homogeneity, clinical presentations differ dramatically. We used molecular...

Objectives To describe the clinical presentation of lymphatic malformations (LM) and genotypically associated disorders and to summarize the recent literature regarding the genetic etiology of LM and provide a biologic correlation to medical and surgical management. Results LM are congenital lesions derived from a developmental abnormality of the...

Exposure to toxicants leads to cumulative molecular changes that over time increase a subject's risk of developing urothelial carcinoma (UC). To assess the impact of arsenic exposure at a time progressive manner, we developed and characterized a cell culture model and tested a panel of miRNAs in urine samples from arsenic exposed subjects, UC patie...

Background: We hypothesize that gene deregulation caused by aberrant miRNA expression may play a role in arsenic-induced transformation. To confirm this hypothesis and to identify the molecular mechanisms involved, we developed a cell culture model that permit us to study the progressive, transforming effects of arsenic in uro-epithelial cell behav...