VACTERL Association in a Male Infant with an Additional Genomic Segment on Chromosome 17p

The case of a term Thai male infant with VACTERL anomalies including imperforate anus, atrial septal defect, tracheo-esophageal (TE) fistula, and horseshoe kidney with bilateral hydronephrosis whose chromosome study revealed an additional genomic segment of unknown origin on the short arm of chromosome 17 is reported. The karyotype is described as 46, XY, add (17) (p13), which has never been previously reported in VACTERL association

Overall expression of beta-catenin outperforms its nuclear accumulation in predicting outcomes of colorectal cancers

AIM: To examine the expression of beta-catenin in colorectal cancer and look for association with other clinico-pathological parameters

Assessment of caspase activity and colony formation after reconstitution with mutant <i>NTRK3</i> in RKO.

<p>The three mutant <i>NTRK3</i> constructs contain <i>NTRK3</i> mutants found in primary human CRC. <b>A.</b> The expression of reconstituted wild-type <i>NTRK3</i> (<i>WT</i>), <i>NTRK3-G608S (G608S)</i>, <i>NTRK3-I695V (I695V)</i> and <i>NTRK3-L760I (L760I)</i> was confirmed by western blotting. <b>B.</b> Apoptosis was assessed by normalized caspase 3 and 7 activity in the RKO cell line 48 hours after transfection with <i>WT</i>, <i>G608S</i>, <i>I695V</i> and <i>L760I NTRK3</i> constructs. <b>C.</b> Soft agar colony formation was assessed in stably-transfected RKO cells after 2 weeks. Results are plotted as the mean colony numbers from three independent experiments. <i>L760I</i> did not induce apoptosis (<b>B</b>) or suppress colony formation (<b>C</b>), whereas <i>WT</i>, <i>G608S</i> and <i>I695V</i> did. Thus, the <i>G608S</i> and <i>I695V</i> mutations appear to be passenger mutations. GUS was used as the control vector to normalize for nonspecific effects of the transfection on apoptosis. The asterisks indicate statistically significant differences, p<0.05 as determined by a 2-sided Mann-Whitney rank sum test.</p

Clinical, pathological, and molecular characteristics of CRCs that carry methylated <i>NTRK3</i> and unmethylated <i>NTRK3</i>.

<p>Clinical, pathological, and molecular characteristics of CRCs that carry methylated <i>NTRK3</i> and unmethylated <i>NTRK3</i>.</p

Assessment of normalized caspase 3 and 7 activity after reconstitution of <i>NTRK3</i> in HCT116 (A), RKO (B) and HT29 (C) cells.

<p>NTRK3 induces caspase activity in HCT116 (MSI), RKO (CIMP) and HT29 (MSS) cells, and NT-3 (100 ng/mL) inhibits this effect in all three cell lines. DMSO is the vehicle control for NT-3, and GUS is the control vector (pDEST27-GUS) used to normalize for nonspecific effects of the transfection on caspase activity. The caspase activity in the GUS transfected cells treated with DMSO was used to normalize the results from the other experimental groups. The asterisks indicate statistically significant differences, <i>p</i><0.05 as determined by a 2-sided Mann-Whitney rank sum test.</p

Bisulfite sequencing results of representative methylated and unmethylated samples as determined by the <i>NTRK3</i> MethyLight (qMSP) assay.

<p>The black boxes indicate methylated CpG dinucleotides, and the white boxes represent unmethylated CpG dinucleotides. Each row depicts the sequencing results for a single clone. <b>A.</b> Schematic diagram of the 5′ end of the <i>NTRK3</i> gene showing the location of the qMSP and bisulfite sequencing primers (TSS: transcriptional start site). <b>B.</b> Results of bisulfite sequencing of DNA from colon cancer cell lines representative of different molecular subtypes: RKO is a CpG island methylator phenotype (CIMP) cell line, HCT116 is microsatellite unstable (MSI) line, and HT29 is a microsatellite stable (MSS) line. These cell lines have dense methylation of <i>NTRK3</i>. <b>C.</b> Representative case of normal colon, which carries unmethylated <i>NTRK3</i>. <b>D. and E.</b> Representative cases of adenomas and adenocarcinomas that carry either methylated or unmethylated <i>NTRK3</i> are shown.</p