Frameshift Mutations in the Mononucleotide Repeats of TAF1 and TAF1L Genes in Gastric and Colorectal Cancers with Regional Heterogeneity
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 apopto...
Saved in:
Published in | Pathology oncology research Vol. 23; no. 1; pp. 125 - 130 |
---|---|
Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Dordrecht
Springer Netherlands
2017
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1219-4956 1532-2807 |
DOI: | 10.1007/s12253-016-0107-0 |