Of the 1352 samples in the cohort, which were provided by multiple collaborators, four samples of breast tissue for which DNA was analyzed were a part of another study. Since these samples did not go through the same rigorous screening process, including pathology review and extraction of DNA from paraffin tissues, that was applied to all other samples, the authors are less confident in their exact identity and have decided to retract them from the study. This does not change the message of the paper, but results in changes in and in one pie chart in Figure 2E, that for breast cancer. The corrected figure parts are below. In addition, the supplemental material containing sample information has been updated online.
Background-Surgical resection is the recognised treatment of choice for patients with stage I or II non-small cell lung cancer (NSCLC). In the UK surgical resection rates have remained far lower (<10%) than those achieved in Europe and the USA (>20%), despite the recent introduction of fast access investigation units. It remains unclear therefore why UK surgical resection rates lag so far behind those of other countries. Methods-A new quick access two stop investigation service was established at Papworth in November 1995 to investigate all patients presenting to any of three surrounding health districts with suspected lung cancer. Once staging was complete, all patients with confirmed lung cancer were reviewed by a multidisciplinary team which included an oncologist and a thoracic surgeon. Time from presentation to definitive treatment and surgical resection rates were reviewed. Results-Two hundred and nine (76%) of a total of 275 consecutive patients investigated had confirmed lung cancer (28 small cell, 181 non-small cell). Of the remainder, eight patients (2%) had metastatic disease, four (1%) had other thoracic malignancy (thymoma, mesothelioma), four patients (1%) had benign thoracic tumours, and 50 (18%) had other non-malignant diseases. Of the 181 patients with non-small cell primary lung cancer, 47 (25%) underwent successful surgical resection, of whom 59% had stage I and 21% stage II disease. The failed thoracotomy rate was 11%. Median time from presentation at the peripheral clinic to surgical resection was 5 weeks (range 1-13). Conclusion-Quick access investigation, high histological confirmation rates, routine CT scanning, and review of every patient with confirmed lung cancer by a thoracic surgeon led to a substantial increase in the successful surgical resection rate. These results support the growing concern that many patients with operable tumours are being denied the chance of curative surgery in our present system. (Thorax 1998;53:445-449)
The identification of new biomarkers to differentiate between indolent and aggressive prostate tumors is an important unmet need. We examined the role of THOR (TERT Hypermethylated Oncological Region) as a diagnostic and prognostic biomarker in prostate cancer (PCa).We analyzed THOR in common cancers using genome-wide methylation arrays. Methylation status of the whole TERT gene in benign and malignant prostate samples was determined by MeDIP-Seq. The prognostic role of THOR in PCa was assessed by pyrosequencing on discovery and validation cohorts from patients who underwent radical prostatectomy with long-term follow-up data.Most cancers (n = 3056) including PCa (n = 300) exhibited hypermethylation of THOR. THOR was the only region within the TERT gene that is differentially methylated between normal and malignant prostate tissue (p < 0.0001). Also, THOR was significantly hypermethylated in PCa when compared to paired benign tissues (n = 164, p < 0.0001). THOR hypermethylation correlated with Gleason scores and was associated with tumor invasiveness (p = 0.0147). Five years biochemical progression free survival (BPFS) for PCa patients in the discovery cohort was 87% (95% CI 73–100) and 65% (95% CI 52–78) for THOR non-hypermethylated and hypermethylated cancers respectively (p = 0.01). Similar differences in BPFS were noted in the validation cohort (p = 0.03). Importantly, THOR was able to predict outcome in the challenging (Gleason 6 and 7 (3 + 4)) PCa (p = 0.007). For this group, THOR was an independent risk factor for BPFS with a hazard-ratio of 3.685 (p = 0.0247). Finally, THOR hypermethylation more than doubled the risk of recurrence across all PSA levels (OR 2.5, p = 0.02).
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