<i>In silico</i> prediction of the <i>CDH1</i> p.T560R variant.

<p>Prediction of the potential effects of the <i>CDH1 c</i>.<i>1679 C>G</i> (p.T560R) alteration on normal mRNA splicing. Top panel: reference sequence; bottom panel: mutated sequence. The text at the left of each panel represents the names of the tools used to predict splice site strength. The number ranges indicate the strength of each target sequence in each prediction tool with the upper range being the perfect match. The reference sequence and mutated sequences are shown at the bottom of each panel with nucleotide positions indicated above. Blue vertical bars indicate 5’ (donor) site. The height of each bar is proportional to the maximum possible score computed by the corresponding algorithm.</p

Patient pedigree, <i>CDH1</i> mutation and H&E image of diffuse gastric cancer.

<p>(A) The patient (indicated with the arrow head) is a 50 year old man who was diagnosed with gastric cancer at the age of 50. In his generation, three members were diagnosed with gastric cancers (one brother died of gastric cancer at 45, another brother was diagnosed with gastric cancer at 63). All three brothers affected with gastric cancer were determined to have the <i>CDH1 c</i>.<i>1679 C>G</i> p.T560R variant. (B) our patient’s germline <i>CDH1</i> sequencing demonstrating the <i>CDH1 c</i>.<i>1679C>G</i> variant. (C) Haematoxylin and eosin stain (H&E stain) of patient’s biopsy specimen showing infiltrating adenocarcinoma poorly differentiated with mucinous and signet ring cell features. The signet ring cells are characteristic of hereditary diffuse gastric cancer (HDGC). They contain large amount of mucin which pushes the nucleus to the cell periphery (see arrows).</p

<i>CDH1 c</i>.<i>1679 C>G</i> (p.T560R) mutant allele creates a novel splice site that results in a 32 nucleotide deletion of the 3’ end of exon 11.

<p>(A) Sequence adjacent to wild type allele, <i>CDH1 c</i>.<i>1679 C</i>, indicating normal splice site. Electropherogram data of normally spliced cDNA with wild type allele highlighted in blue. (B) Sequence adjacent to mutant allele, <i>CDH1 c</i>.<i>1679 G</i>, indicating aberrant splice site produced by mutant allele (solid lines) and location of normal splice site (dashed lines). Electropherogram data of aberrantly spliced cDNA with the mutant allele highlighted in light blue.</p