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Head and neck cancer has poor overall survival. Patients with head and neck cancer more frequently develop second primary tumors than do patients with other cancers, leading to a poor prognosis. In this study, we used next-generation sequencing to analyze and compare mutations between first tumors and second tumors in oral cancer. We retrieved tumor tissues collected from 13 patients who were diagnosed twice as having cancer. We used driver gene and trunk mutations to distinguish between recurrent cancer and primary cancer in oral cancer. We observed unique driver gene mutations in three patients with an initial clinical diagnosis of recurrent cancer; hence, we believe that the corresponding patients had primary cancer. Four patients with an initial clinical diagnosis of primary cancer were found to actually have recurrent cancer according to our results. Genetic testing can be used to enhance the accuracy of clinical diagnosis. [ABSTRACT FROM AUTHOR]

Background: Congenital dyserythropoiesis anemia type Ia (OMIM:224120), is a rare hereditary anemia. The diagnosis is difficult to make and usually delayed in part due to its rarity and nonspecific clinical manifestations. Methods: Whole exome sequencing was applied for the genetic diagnosis of a 12‐year‐old boy who has suffered from hemolytic anemia since birth and who requires regular transfusions. Sanger sequencing of the variants detected in whole exome sequencing was performed in the patient and his parents. Results: Compound heterozygous mutations of CDAN1 gene, including one previously reported and one novel mutation, which is a splicing change, were detected in the whole exome sequencing and confirmed by Sanger sequencing. The autosomal recessive inheritance was confirmed by pedigree analysis. Conclusion: To our knowledge, this is the first case report of congenital dyserythropoiesis anemia type Ia with genetic diagnosis to be located in Taiwan. Because of the rarity of CDA Ia and the overlapping of the clinical manifestations with other hereditary anemias, the next‐generation sequencing approach is effective for conclusive diagnosis of CDA Ia. [ABSTRACT FROM AUTHOR]

The genomic landscape of breast cancer (BC) is complex. The purpose of this study was to decipher the mutational profiles of Taiwanese patients with BC using next-generation sequencing. We performed whole-exome sequencing on DNA from 24 tumor tissue specimens from BC patients. Sanger sequencing was used to validate the identified variants. Sanger sequencing was also performed on paired adjacent nontumor tissues. After genotype calling and algorithmic annotations, we identified 49 deleterious variants in canonical cancer-related genes in our BC cohort. The most frequently mutated genes were PIK3CA (16.67%), FKBP9 (12.5%), TP53 (12.5%), ATM (8.33%), CHEK2 (8.33%), FOXO3 (8.33%), NTRK1 (8.33%), and NUTM2B (8.33%). Seven mutated variants (ATR p.V1581fs, CSF1R p.R579Q, GATA3 p.T356delinsTMKS, LRP5 p.W389*, MAP3K1 p.T918fs, MET p.K1161fs, and MTR p.P1178S) were novel variants that are not present in any gene mutation database. After grouping the samples according to molecular subtype, we found that the cell cycle, MAPK, and chemokine signaling pathways in the luminal A subtype of BC; the focal adhesion, axon guidance, and endocytosis pathways in the luminal B subtype; and amyotrophic lateral sclerosis in the basal-like subtype were exclusively altered. Survival curve analysis showed that the presence of the MAPK signaling pathway and endocytosis mutations were correlated with a poor prognosis. These survival data were consistent with cBioPortal analyses of 2,051 BC cases. We discovered novel mutations in patients with BC. These results have implications for developing strategic, adjuvant, and gene-targeted therapies. [ABSTRACT FROM AUTHOR]

Purpose: Analysis of circulating tumor DNA (ctDNA) offers an unbiased and noninvasive way to assess the genetic profiles of tumors. This study aimed to analyze mutations in ctDNA and their correlation with tissue mutations in patients with a variety of cancers.Methods: We included 21 cancer patients treated with surgical resection for whom we collected paired tissue and plasma samples. Next-generation sequencing (NGS) of all exons was performed in a targeted human comprehensive cancer panel consisting of 275 genes.Results: Six patients had at least one mutation that was concordant between tissue and ctDNA sequencing. Among all mutations (n = 35) detected by tissue and blood sequencing, 20% (n = 7) were concordant at the gene level. Tissue and ctDNA sequencing identified driver mutations in 66.67% and 47.62% of the tested samples, respectively. Tissue and ctDNA NGS detected actionable alterations in 57.14% and 33.33% of patients, respectively. When somatic alterations identified by each test were combined, the total proportion of patients with actionable mutations increased to 71.43%. Moreover, variants of unknown significance that were judged likely pathogenic had a higher percentage in ctDNA exclusively. Across six representative genes (PIK3CA, CTNNB1, AKT1, KRAS, TP53, and MET), the sensitivity and specificity of detection using mutations in tissue sample as a reference were 25 and 96.74%, respectively.Conclusions: This study indicates that tissue NGS and ctDNA NGS are complementary rather than exclusive approaches; these data support the idea that ctDNA is a promising tool to interrogate cancer genetics. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide. Despite curative resection, high recurrence of HCC remains a big threat, leading to poor patient outcomes. Hepatitis B virus (HBV) pre-S mutants, which harbor deletions over pre-S1 and pre-S2 gene segments of large surface proteins, have been implicated in HCC recurrence. Therefore, a reliable approach for detection of pre-S mutants is urgently needed for predicting HCC recurrence to improve patient survival. In this study, we used a next-generation sequencing (NGS)-based platform for quantitative detection of pre-S mutants in the plasma of HBV-related HCC patients and evaluated their prognostic values in HCC recurrence. We demonstrated that the presence of deletions spanning the pre-S2 gene segment and the high percentage of pre-S2 plus pre-S1 + pre-S2 deletions, either alone or in combination, was significantly and independently associated with poor recurrence-free survival and had greater prognostic performance than other clinicopathological and viral factors in predicting HCC recurrence. Our data suggest that the NGS-based quantitative detection of pre-S mutants in plasma represents a promising approach for identifying patients at high risk for HBV-related HCC recurrence after surgical resection in a noninvasive manner. [ABSTRACT FROM AUTHOR]