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Chang-hua, Taiwan

Lin Y.-J.,National Tsing Hua University | Chen Y.-T.,National Tsing Hua University | Hsu S.-N.,National Tsing Hua University | Peng C.-H.,Chang Gung Memorial Hospital | And 5 more authors.
PLoS ONE | Year: 2014

Copy number variation (CNV) has been reported to be associated with disease and various cancers. Hence, identifying the accurate position and the type of CNV is currently a critical issue. There are many tools targeting on detecting CNV regions, constructing haplotype phases on CNV regions, or estimating the numerical copy numbers. However, none of them can do all of the three tasks at the same time. This paper presents a method based on Hidden Markov Model to detect parent specific copy number change on both chromosomes with signals from SNP arrays. A haplotype tree is constructed with dynamic branch merging to model the transition of the copy number status of the two alleles assessed at each SNP locus. The emission models are constructed for the genotypes formed with the two haplotypes. The proposed method can provide the segmentation points of the CNV regions as well as the haplotype phasing for the allelic status on each chromosome. The estimated copy numbers are provided as fractional numbers, which can accommodate the somatic mutation in cancer specimens that usually consist of heterogeneous cell populations. The algorithm is evaluated on simulated data and the previously published regions of CNV of the 270 HapMap individuals. The results were compared with five popular methods: PennCNV, genoCN, COKGEN, QuantiSNP and cnvHap. The application on oral cancer samples demonstrates how the proposed method can facilitate clinical association studies. The proposed algorithm exhibits comparable sensitivity of the CNV regions to the best algorithm in our genome-wide study and demonstrates the highest detection rate in SNP dense regions. In addition, we provide better haplotype phasing accuracy than similar approaches. The clinical association carried out with our fractional estimate of copy numbers in the cancer samples provides better detection power than that with integer copy number states. © 2014 Lin et al. Source

Peng C.-H.,Chang Gung Memorial Hospital | Liao C.-T.,Head and Neck Surgery | Liao C.-T.,Head and Neck Oncology Group | Ng K.-P.,National Tsing Hua University | And 8 more authors.
Oncotarget | Year: 2015

Background: Ultra-deep targeted sequencing (UDT-Seq) has advanced our knowledge on the incidence and functional significance of somatic mutations. However, the utility of UDT-Seq in detecting copy number alterations (CNAs) remains unclear. With the goal of improving molecular prognostication and identifying new therapeutic targets, we designed this study to assess whether UDT-Seq may be useful for detecting CNA in oral cavity squamous cell carcinoma (OSCC). Methods: We sequenced a panel of clinically actionable cancer mutations in 310 formalin-fixed paraffin-embedded OSCC specimens. A linear model was developed to overcome uneven coverage across target regions and multiple samples. The 5-year rates of secondary primary tumors, local recurrence, neck recurrence, distant metastases, and survival served as the outcome measures. We confirmed the prognostic significance of the CNA signatures in an independent sample of 105 primary OSCC specimens. Results: The CNA burden across 10 targeted genes was found to predict prognosis in two independent cohorts. FGFR1 and PIK3CA amplifications were associated with prognosis independent of clinical risk factors. Genes exhibiting CNA were clustered in the proteoglycan metabolism, the FOXO signaling, and the PI3K-AKT signaling pathways, for which targeted drugs are already available or currently under development. Conclusions: UDT-Seq is clinically useful to identify CNA, which significantly improve the prognostic information provided by traditional clinicopathological risk factors in OSCC patients. Source

Chen S.-C.,Chang Gung Institute of Technology | Chen S.-C.,Head and Neck Oncology Group | Liao C.-T.,Head and Neck Surgery | Liao C.-T.,Chang Gung University | And 3 more authors.
Oral Oncology | Year: 2011

Surgical and radiation therapy for oral squamous cell carcinoma (OSCC) may generate orofacial pain. The aims of this study were to (1) characterize the pain experienced by people with orofacial pain, and (2) determine the factors associated with changes in orofacial pain in OSCC patients during the postoperative and post-radiation therapy periods. The study had a prospective longitudinal design with consecutive sampling. Seventy-two eligible patients were recruited from the outpatient department of otolaryngology, head and neck cancer, and radiation therapy of a medical center in northern Taiwan. A set of questionnaires was used for patient assessment, including the University of California San Francisco Oral Cancer Pain Questionnaire, Symptom Severity Scale, Hospital Anxiety and Depression Scale, and Karnofsky's Performance Status Index. Patients were assessed at two time points: 1 month after surgery (T1) and 1 month after completion of radiation treatment (T2). The findings showed that (1) patients reported moderate orofacial pain at both time points; (2) orofacial pain, oral function-related symptoms, and psychological distress were significantly higher at T1 than at T2; and (3) older age, eating difficulty, speech difficulty, and depression were significant predictors of orofacial pain. Oral rehabilitation and relaxation training may reduce orofacial pain in this patient population. © 2010 Elsevier Ltd. All rights reserved. Source

Chen S.-C.,Chang Gung Institute of Technology | Chen S.-C.,Head and Neck Oncology Group | Lai Y.-H.,National Taiwan University | Liao C.-T.,Head and Neck Surgery | And 6 more authors.
Oral Oncology | Year: 2010

The purposes of this study were to (1) examine changes in symptom severity and depression within 3 months of first undergoing radiation therapy (RT) or concurrent chemoradiation therapy (CCRT), and (2) identify factors involved in changes in symptom severity in newly diagnosed oral cavity cancer patients undergoing post-operative RT or CCRT. A prospective panel survey was conducted to assess changes in symptoms, depression, and disease- or treatment-related characteristics within 3 months of beginning RT or CCRT (pre-treatment and 1, 2, and 3 months from first receiving RT). A total of 76 eligible oral cavity cancer patients were recruited from the outpatient radiation department of a medical center in northern Taiwan. The results showed mild-to-moderate overall symptom and depression levels during treatment, with the five most distressing symptoms being swallowing difficulty, poor appetite, oral mucositis, pain, and fatigue. The severity of symptoms and depression peaked at ∼2 months from beginning RT or CCRT (T3). Changes in overall symptom severity were found to be significantly related to patients' radiation dose and depression level. These results can help advance understanding of changes in symptoms and facilitate prevention and management of symptoms associated with RT or CCRT. Psychological distress, particularly, depression, requires careful monitoring and management in oral cavity cancer patients undergoing RT or CCRT. © 2010 Elsevier Ltd. All rights reserved. Source

Lee L.-Y.,China Medical University Beigang Hospital | Lee L.-Y.,National Taipei University of Nursing and Health Sciences | Chen S.-C.,Chang Gung University | Chen S.-C.,Head and Neck Oncology Group | And 7 more authors.
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology | Year: 2015

Objective The aims of this study were to investigate the following in patients with head and neck cancer (HNC): (1) factors related to trismus that predict the development of trismus, (2) factors affecting quality of life and measurements of these factors, and (3) comparison of these findings in patients with and without trismus to evaluate the effects of trismus on quality of life. Methods This cross-sectional study included the questionnaires: the Hospital Anxiety and Depression Scale (HADS) - Depression Subscale, the Chewing Function Questionnaire (CFQ), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Head and Neck Cancer Module (EORTC QLQ-HN35). A scaled ruler was used to measure maximal intercisal opening (MIO). Results Of the 104 patients in the study, 8.7% had clinical depression. The average MIO was 35.81 mm, and 47.1% of patients had trismus. Moderate levels of chewing dysfunction with regard to different types of food were noted. Lower body mass index, chemoradiotherapy treatment, longer time since treatment completion, and higher radiation dose were significantly associated with trismus. Such patients had significantly lower head and neck-specific quality of life in terms of social contact, sexuality, teeth, mouth opening, dry mouth, feeling ill, nutritional supplement, and weight loss. Conclusions Patients with trismus should be provided mouth opening exercises after treatment and programs to improve trismus and quality of life. © 2015 Elsevier Inc. Source

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