title: Frameshift Mutations in the Mononucleotide Repeats of TAF1 and TAF1L Genes in Gastric and Colorectal Cancers with Regional Heterogeneity.
abstract: Initiation of transcription by RNA polymerase II requires TATA-box-binding protein (TBP)-associated factors (TAFs). TAF1 is a major scaffold by which TBP and TAFs interact in the basal transcription factor. TAF1L is a TAF1 homologue with 95 % amino acid identity with TAF1. TAF1 is involved in apoptosis induction and cell cycle regulation, but roles of TAF1 and TAF1L in tumorigenesis remain unknown. The aim of this study was to explore whether TAF1 and TAF1L genes were mutated in gastric (GC) and colorectal cancers (CRC). In a public database, we found that TAF1 and TAF1L genes had mononucleotide repeats in the coding sequences that might be mutation targets in the cancers with microsatellite instability (MSI). We analyzed the mutations in 79 GC and 124 CRC by single-strand conformation polymorphism analysis and DNA sequencing. In the present study, we found TAF1 frameshift mutations (3.8 % of CRC with MSI-H) and TAF1L frameshift mutations (2.9 % of GC and 3.8 % of CRC with MSI-H). These mutations were not found in stable MSI/low MSI (MSS/MSI-L) (0/90). In addition, we analyzed intratumoral heterogeneity (ITH) of TAF1 and TAF1L frameshift mutations in 16 CRC and found that two and one CRC harbored regional ITH of TAF1 and TAF1L frameshift mutations, respectively. Our data indicate that TAF1 and TAF1L genes harbored not only somatic mutations but also mutational ITH, which together might play a role in tumorigenesis of GC and CRC with MSI-H. Our results also suggest that ultra-regional mutation analysis is required for a comprehensive evaluation of mutation status in these tumors.
authors: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, South Korea.
authors: Hye Rim
authors: HR
authors: Oh
authors: Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, 137-701, South Korea.
authors: Chang Hyeok
authors: CH
authors: An
authors: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, South Korea.
authors: Nam Jin
authors: NJ
authors: Yoo
authors: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, South Korea. suhulee@catholic.ac.kr.
authors: Sug Hyung
authors: SH
authors: Lee
mesh_terms: D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics; D016368:Frameshift Mutation / Q000235:genetics*; D051548:Histone Acetyltransferases / Q000235:genetics*; D006801:Humans; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics*; D035362:Transcription Factor TFIID / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C472868:TAF1L protein, human; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C069001:TATA-binding protein associated factor 250 kDa
keywords: Basal transcription component; Cancers; Microsatellite instability; Mutation; TAF1; TAF1L