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Initiation of transcription for ribosomal RNA (rRNA) by RNA polymerase I requires TATA-binding protein (TBP) and TBP-associated factors (TAF1A, TAF1B and TAF1C). p53 tumour suppressor inhibits rRNA transcription by blocking TAF1C-UBF interaction, but alterations of TAF1C itself in tumorigenesis remain unknown. The aim of this study was to explore whether TAF1C gene was mutated in gastric (GC) and colorectal cancers (CRC).In a public database, we found that TAF1C gene had a mononucleotide repeat (C8) in the coding sequences that might be a mutation target in the cancers with microsatellite instability (MSI). We analysed 79 GC and 124 CRC by single-strand conformation polymorphism and DNA sequencing analyses. In this study, we found TAF1C frameshift mutations (8.8% of GC and 10.1% of CRC with MSI-H), which were not found in stable MSI/low MSI (MSS/MSI-L) (0/90). In addition, we analysed intratumoural heterogeneity (ITH) of TAF1C frameshift mutations in 16 CRC and found that three CRC (18.8%) harboured regional ITH of the TAF1C frameshift mutations. Our results indicate that TAF1C gene harboured not only somatic frameshift mutations but also the mutational ITH, which together might play a role in tumourigenesis of GC and CRC. Our data also suggest that multi-regional mutation analysis is needed for a better evaluation of the mutation status in CRC.

Evasion of apoptosis is a feature of cancer cells. As a mechanism of apoptosis inactivation in cancer cells, somatic mutations of pro-apoptotic genes have been reported in many cancers. Caspase-10 is an initiation-phase caspase, and somatic mutation of CASP10 that encodes caspase-10 has been found in non-Hodgkin's lymphoma and gastric carcinoma.The aim of this study was to explore whether CASP10 gene is somatically mutated in colon, breast, lung, and hepatocellular carcinomas. We analysed the entire coding region and all splice sites of CASP10 in 47 colon, 47 breast, 47 lung, and 47 hepatocellular carcinomas by a single-strand conformation polymorphism (SSCP) assay.We found two CASP10 mutations in the colon cancers (2/47; 4.3%), but none in breast, lung or hepatocellular carcinomas. One mutation [c.41AC (p.Lys14Thr)] was a missense mutation, while the other was a substitution mutation in a splice site (c.684 + 4GA). The colon cancer with the CASP10 missense mutation harboured additional CASP gene mutations (CASP3, 7 and 8).Our data indicate that somatic mutation of CASP10 is rare in colon, breast, lung, and hepatocellular carcinomas. However, the data also suggest that CASP10 mutation might contribute to the pathogenesis of some colon carcinomas together with other CASP gene mutations.

Sir,Microtubules, a major component of the cytoskeleton, are highly dynamic structures. The (–) end of microtubules is anchored at the centrosome matrix, while the (+) end radiates towards the cell...

Summary Aims Activation of nuclear factor-kappa B (NF-κB) signalling is considered a crucial mechanism in the development of cancers. Caspase-associated recruitment domain 6 (CARD6) is a protein that activates NF-κB signalling evoked by RIP1, RIP2, Bcl-10 and MEKK. In this study, we analysed tissue expression of CARD6 protein in oesophageal squamous cell carcinoma (ESCC), gastric adenocarcinomas (GC) and colorectal adenocarcinomas (CRC). Methods We analysed the expression of CARD6 protein in 58 ESCC, 100 GC and 103 CRC patients’ tissues by immunohistochemistry using a tissue microarray (TMA) approach. Results We found CARD6 immunostaining in cancer cells of ESCC (41/58; 70.7%), GC (45/100; 45.0%) and CRC (81/103; 78.6%). In the GC, intestinal-type GC (77.8%) showed higher expression of CARD6 than diffuse-type GC (20.0%) and mixed-type GC (50.0%). By contrast, corresponding normal epithelial cells of oesophagus (0%), stomach (8.0%) and colon (5.0%) displayed lower frequencies of CARD6 immunostaining. The CARD6 immunostaining was observed in nucleus/cytoplasm (ESCC) or cytoplasm (GC and CRC). The CARD6 expression was evident from an early TNM stage (stage I). Conclusions The increased expression of CARD6 in ESCC, GC and CRC tissues compared to their corresponding normal cells suggested that neoexpression of CARD6 might be related to activation of NF-κB pathway in the cancers and might play a role in the development of most types of gastrointestinal cancers.

Summary Aims Nuclear factor-kappa B (NF-κB) activation has been recognised as an important mechanism in the development of cancers. However, expression status of NF-κB-related proteins in oesophageal squamous cell carcinoma (ESCC) tissues is largely unknown. In this study, we analysed expressions of NF-κB members (p50/105, p52/p100 and RelA) and IKKe in ESCC tissues. Methods We analysed the expression of p50/105, p52/p100, RelA and IKKe in 58 ESCC patients’ tissues by immunohistochemistry using a tissue microarray (TMA) method. Results Normal oesophageal squamous cells expressed p50/105, p52/p100 and RelA in 5%, 79% and 10% of the tissues in cytoplasm, respectively; however, only p52/p100 was expressed in the nuclei (12%). The cancer tissues expressed p50/105, p52/p100 and RelA in 93%, 95% and 95% in cytoplasm and/or nuclei, respectively. Nuclear immunostainings of NF-κB members p50/105, p52/p100 and RelA, which are considered activation of NF-κB signalling, were observed in 34%, 60% and 26% of the cancers, respectively. IKKe is expressed in cytoplasm in 50% of the normal squamous tissues and 84% of the cancer tissues. However, none of the expression of p50/105, p52/p100, RelA or IKKe was associated with pathological characteristics, including differentiation, depth of invasion and TNM stage. Conclusion The increased nuclear expressions of p50/105, p52/p100 and RelA as well as increased cytoplasmic expression of IKKe in the ESCC tissues compared to the normal squamous cells suggested that over-expression of these proteins may be related to activation of the NF-κB pathway and might play a role in the development of ESCC.