31,34 Consequently, although some patients with germline PTEN mutations present with clinical signs not diagnostic for Cowden syndrome, they should be classified as having PTEN hamartoma tumour syndrome Idelalisib purchase and medically managed as such.10,31 Electronic database information JPS: Online Mendelian Inheritance in Man (OMIM) 174900 SMAD4: OMIM *600993; reference sequence GenBank “type”:”entrez-nucleotide”,”attrs”:”text”:”NM_005359.3″,”term_id”:”34147555″,”term_text”:”NM_005359.3″NM_005359.3; GI34147555 BMPR1A: OMIM *601299; reference sequence GenBank “type”:”entrez-nucleotide”,”attrs”:”text”:”NM_004329.2″,”term_id”:”41349436″,”term_text”:”NM_004329.2″NM_004329.2; GI41349436 PTEN: OMIM *601728; reference sequence GenBank “type”:”entrez-nucleotide”,”attrs”:”text”:”NM_000314.

4″,”term_id”:”110224474″,”term_text”:”NM_000314.4″NM_000314.4; GI110224474 CDH1: OMIM *192090; reference sequence GenBank “type”:”entrez-nucleotide”,”attrs”:”text”:”NM_004360.2″,”term_id”:”14589887″,”term_text”:”NM_004360.2″NM_004360.2; GI14589887 Human Gene Mutation Database, Cardiff: http://www.hgmd.cf.ac.uk/ac/index.php Berkeley Drosophila Genome Project (BDGP): http://www.fruitfly.org/seq_tools/splice.html GeneReviews: http://www.genetests.org/ In summary, we show that large SMAD4 and BMPR1A deletions are present in about 14% of all patients meeting the clinical criteria for JPS. We confirm a strong genotype�Cphenotype correlation regarding gastric polyposis, gastric cancer and HHT in SMAD4 mutation carriers, which should have implications for counselling and clinical surveillance.

In case of any uncertainty or doubtful histological findings, re�\evaluation of the polyp tissue by an experienced pathologist is recommended. As a correct clinical and molecular diagnosis has important consequences for appropriate clinical management, our observations and those of others underline the need for a more extensive analysis of the SMAD4, BMPR1A and PTEN genes in patients with hamartomatous polyposis including mixed polyposis syndromes. Acknowledgements We are grateful to the patients who participated in the study. The study was supported by the German Cancer Aid (Deutsche Krebshilfe e.V. Bonn, project no. 106244).

Abbreviations BDGP – Berkeley Drosophila Genome Project CCS – Cronkhite�CCanada syndrome Cilengitide HHT – hereditary haemorrhagic telangiectasia HMPS – hereditary mixed polyposis syndromes JPS – juvenile polyposis syndrome MLPA – multiplex ligation�\dependent probe amplification OMIM – Online Mendelian Inheritance in Man RT – reverse transcriptase Footnotes Competing interests: None declared.
Advances in surgical technique, including total mesorectal excision and thorough pathohistological work-up of the resected specimen have significantly improved the prognosis of patients with localised rectal cancer during the past two decades.