Whole-Exome Sequencing Analysis of Oral Squamous Cell Carcinoma Delineated by Tobacco Usage Habits.

Oral squamous cell carcinoma (OSCC) is a common cancer of the oral cavity in India. Cigarette smoking and chewing tobacco are known risk factors associated with OSCC. However, genomic alterations in OSCC with varied tobacco consumption history are not well-characterized. In this study, we carried out whole-exome sequencing to characterize the mutational landscape of OSCC tumors from subjects with different tobacco consumption habits. We identified several frequently mutated genes, including TP53, NOTCH1, CASP8, RYR2, LRP2, CDKN2A, and ATM. TP53 and HRAS exhibited mutually exclusive mutation patterns. We identified recurrent amplifications in the 1q31, 7q35, 14q11, 22q11, and 22q13 regions and observed amplification of EGFR in 25% of samples with tobacco consumption history. We observed genomic alterations in several genes associated with PTK6 signaling. We observed alterations in clinically actionable targets including ERBB4, HRAS, EGFR, NOTCH1, NOTCH4, and NOTCH3. We observed enrichment of signature 29 in 40% of OSCC samples from tobacco chewers. Signature 15 associated with defective DNA mismatch repair was enriched in 80% of OSCC samples. NOTCH1 was mutated in 36% of samples and harbored truncating as well as missense variants. We observed copy number alterations in 67% of OSCC samples. Several genes associated with non-receptor tyrosine kinase signaling were affected in OSCC. These molecules can serve as potential candidates for therapeutic targeting in OSCC.

Molecular alterations in oral cancer between tobacco chewers and smokers using serum proteomics.

BACKGROUND: Tobacco exposure (through smoking or chewing) is one of the predominant risk factors associated with the development of oral squamous cell carcinoma (OSCC). Despite the growing number of patients diagnosed with OSCC, there are few circulating biomarkers for identifying individuals at a higher risk of developing the disease. Successful identification of candidate molecular markers for risk assessment could aid in the early detection of oral lesions and potentially be used for community screening of high-risk populations. OBJECTIVE: Identification of differentially expressed proteins in the serum of oral cancer patients which can serve as biomarkers for the diagnosis of the onset of oral cancer among tobacco users. METHODS: We employed a tandem mass tag (TMT)-based quantitative proteomics approach to study alterations in the serum proteomes of OSCC patients based on their tobacco exposure habits (chewing and smoking) compared to healthy individuals with no history of using any form of tobacco or any symptoms of the disease. RESULTS: Mass spectrometry-based analysis resulted in the identification of distinct signatures in the serum of OSCC patients who either chewed or smoked tobacco. Pathway analysis revealed opposing effects of dysregulated proteins enriched in the complement-coagulation signaling cascades with a high expression of the Serpin family of proteins observed in OSCC patients who chewed tobacco compared to healthy individuals whereas these proteins showed decreased levels in OSCC patients who smoked. ELISA-based validation further confirmed our findings revealing higher expression of SERPINA6 and SERPINF1 across serum of OSCC patients who chewed tobacco compared to healthy individuals. CONCLUSIONS: This study serves as a benchmark for the identification of serum-based protein markers that may aid in the identification of high-risk patients who either chew tobacco or smoke tobacco.

Feasibility and Reliability of Microvascular Reconstruction in the Vessel-depleted Previously Operated Neck.

BACKGROUND: Microvascular reconstruction of defects in the head and neck has always been a challenge in patients who have undergone previous neck dissection, owing to the prior resection of potential recipient blood vessels used for free flap perfusion. OBJECTIVE: The objective of the study is to evaluate the reliability and safety of free flap reconstruction in patients who have had previous neck dissection. MATERIALS AND METHODS: Twenty-four free flaps were performed in 22 patients with a previous history of neck dissection for head-and-neck squamous cell carcinoma. These included patients who underwent salvage surgery for recurrent cancer as well as patients undergoing secondary reconstruction following previous oncological resections. Flap includes 12 radial forearm free flaps, 5 fibula flaps, 1 rectus abdominis flap, and 6 anterolateral thigh flaps. RESULTS: In cases with the previous history of selective neck dissection, recipient vessels on the ipsilateral/same side of the previously operated neck were used, while contralateral vessels were used in patients with a history of modified radical or radical neck dissection. Vein grafts were not necessary, except for one case. In our series, we did not have any flap loss or considerable increase in operative time. CONCLUSIONS: Free flap reconstruction of head-and-neck defects is highly successful in patients with a history of previous neck dissection, despite a relative scarcity of recipient blood vessels. Careful planning and relying on flaps with a long vascular pedicle obviates the need to perform a suitable vein graft. In our present series, careful planning and the right choice of a free flap with a long vascular pedicle contributes to the absence of free flap failure. In our experience, previous neck dissection should not be considered as a contraindication to microvascular reconstruction of previously operated oncologic defects.

Idiopathic periscapular tumoral calcinosis mimicking and presenting as extraskeletal chondromatous tumor.

Tumoral calcinosis is a rare, benign condition of extra-osseous calcification. The term tumoral calcinosis has been liberally and imprecisely used to describe any massive collection of periarticular calcification.It is important to diagnose and differentiate it from other similar conditions causing extra-osseous calcification. The authors report here one such case having tumoral calcinosis around scapula mimicking as chondromatous tumor.