Publications by authors named "N Hearle"
Background: Despite previous studies, uncertainty has persisted about the role of thymidylate synthase (TS) and p53 status as markers of prognosis in colorectal cancer (CRC).
Patients And Methods: A total of 967 patients accrued to a large adjuvant trial in CRC were included in a prospectively planned molecular substudy, and of them, 59% had rectal cancer and about 90% received adjuvant chemotherapy (either systemically or randomly allocated to intraportal 5-fluorouracil infusion or both). TS and p53 status were determined, blinded to any clinical data, by immunohistochemistry using a validated polyclonal antibody or the DO-7 clone, respectively, and their relationships with overall survival were examined.
Background: Peutz-Jeghers syndrome (PJS) is caused by germline STK11 mutations and characterised by gastrointestinal polyposis. Although small bowel intussusception is a recognised complication of PJS, risk varies between patients.
Objective: To analyse the time to onset of intussusception in a large series of PJS probands.
Background: Although an increased cancer risk in Peutz-Jeghers syndrome is established, data on the spectrum of tumors associated with the disease and the influence of germ-line STK11/LKB1 (serine/threonine kinase) mutation status are limited.
Experimental Design: We analyzed the incidence of cancer in 419 individuals with Peutz-Jeghers syndrome, and 297 had documented STK11/LKB1 mutations.
Results: Ninety-six cancers were found among individuals with Peutz-Jeghers syndrome.
Background: Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant cancer predisposition syndrome characterised by oro-facial pigmentation and hamartomatous polyposis of the gastrointestinal tract. A causal germline mutation in STK11 can be identified in 30% to 80% of PJS patients.
Methods: Here we report the comprehensive mutational analysis of STK11 in 38 PJS probands applying conventional PCR based mutation detection methods and the recently introduced MLPA (multiplex ligation dependent probe amplification) technique developed for the identification of exonic deletions/duplications.
Background: Germline mutations or large-scale deletions in the coding region and splice sites of STK11/LKB1 do not account for all cases of Peutz-Jeghers syndrome (PJS). It is conceivable that, on the basis of data from other diseases, inherited variation in promoter elements of STK11/LKB1 may cause PJS.
Results: Phylogenetic foot printing and transcription factor binding site prediction of sequence 5' to the coding sequence of STK11/LKB1 was performed to identify non-coding sequences of DNA indicative of regulatory elements.