Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma.

In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched. We next extended our analysis on a prioritized sub-set of 37 mutated genes plus top 5 mutated cancer genes listed in COSMIC using a custom designed HaloPlex target enrichment panel with an additional 88 NPC samples. Our analysis identified 160 additional non-synonymous mutations in 37/42 genes in 66/88 samples. Of these, 99/160 mutations within potentially druggable pathways were further selected for validation. Sanger sequencing revealed that 77/99 variants were true positives, giving an accuracy of 78%. Taken together, our study indicated that ~72% (n = 71/98) of NPC samples harbored mutations in one of the four cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair) which may be potentially useful as predictive biomarkers of response to matched targeted therapies.

A Genome Wide Study of Copy Number Variation Associated with Nasopharyngeal Carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV). CNV is an inherent structural variation that has been found to be involved in cancer predisposition. METHODS: A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124). RESULTS: Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (Pcombined = 1.54x10-5; odds ratio (OR) = 7.27; 95% CI = 2.96-17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (Pcombined = 1.29x10-3; OR = 4.21; 95% CI = 1.75-10.11) overlapping MICA/HCP5/HCG26 genes. CONCLUSION: Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.

Cervical schwannoma: report of four cases.

Extracranial schwannomas in the head and neck region are rare neoplasms. The tumours often present as asymptomatic, slowly enlarging lateral neck masses and determination of the nerve origin is not often made until the time of surgery. Preoperative diagnosis maybe aided by imaging studies such as magnetic resonance imaging or computed tomography, while open biopsy is no longer recommended. The accepted treatment for these tumors is surgical resection with preservation of the neural pathway. We report four cases of cervical schwannomas that we encountered at our center during four years of period. The clinical features, diagnosis and origin, management and pathological findings of these benign tumors are discussed.

Review of ear, nose and throat foreign bodies in Sarawak General Hospital. A five year experience.

OBJECTIVE: Ear, nose and throat foreign bodies are common in ENT clinical practice. This study was designed to establish the local data of otorhinolaryngeal foreign bodies in term of prevalence among paediatric and adult groups, the clinical features, types of foreign body at different sites, and laterality of foreign bodies. METHOD: This study was carried out at ENT department, Sarawak General Hospital, Malaysia, from 1st January 2005 to 31st December 2009. A total of 1084 cases were included and statistically analyzed. RESULT: Ear foreign bodies showed the highest incidence which was consisted of 480 (44.3%) cases, followed by nose in 270 (24.9%) cases, pharynx in 251 (23.2%) cases, esophagus in 57 (5.3%) cases and laryngo-tracheobronchial tree in 26 (2.4%) cases. Otorhinolaryngeal foreign bodies occurred more frequently in 0-10 year old age group which constituted 651 (60.1%) cases. The descending order of frequency for foreign body sites in adult was pharynx (17.2%), ear (12.8%), esophagus (3.1%), nose (1.7%) and laryngo-tracheobronchial tree (1.1%). The type of foreign bodies varies with age group and site of foreign body lodgement. In general, common foreign bodies in both adult and children were food related, with the additional of small objects such as plastic toy in paediatric group. CONCLUSION: Otorhinolaryngeal foreign bodies were found more frequently in children. The types of foreign body were different from age group and sites of foreign body lodgement. The local food constituted the highest incidence of ear, nose, and throat foreign bodies with additional of plastic toys in paediatric group.

Cervical Schwannoma: Report of Four Cases

Extracranial schwannomas in the head and neck region are rare neoplasms. The tumours often present as asymptomatic, slowly enlarging lateral neck masses and determination of the nerve origin is not often made until the time of surgery. Preoperative diagnosis maybe aided by imaging studies such as magnetic resonance imaging or computed tomography, while open biopsy is no longer recommended. The accepted treatment for these tumors is surgical resection with preservation of the neural pathway. We report four cases of cervical schwannomas that we encountered at our center during four years of period. The clinical features, diagnosis and origin, management and pathological findings of these benign tumors are discussed.

Silent sinus syndrome due to a maxillary mucocele.

Silent sinus syndrome is a rare clinical condition in which patients present with spontaneous enophthalmos and hypoglobus secondary to collapse of orbital floor due to chronic subclinical maxillary sinusitis. It is postulated that obstruction of the osteomeatal complex lead to negative antrum pressure which causes the maxillary sinus atelectasis.