Showing papers by "Nam Jin Yoo published in 2017"

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.

Intratumoral Heterogeneity of Frameshift Mutations in MECOM Gene is Frequent in Colorectal Cancers with High Microsatellite Instability.

Abstract: MECOM gene, also known as EVI, encodes a transcriptional regulator involved in hematopoiesis, apoptosis, development and proliferation. In blood system, MECOM is considered an oncogene, but in solid tumors it has both oncogenic and tumor suppressor activities. Low frequent somatic mutations of MECOM have been detected in many cancers including colorectal cancers (CRC), but the mutation status with respect to the microsatellite instability (MSI) has not been studied. There is an A7 mononucleotide repeat in MECOM coding sequences that could be a mutation target in the cancers with MSI. We analyzed the A7 of MECOM in 79 CRCs with high MSI (MSI-H) and 65 microsatellite stable/low MSI (MSS/MSI-L) CRCs by single-strand conformation polymorphism analysis and DNA sequencing. Overall, we found MECOM frameshift mutations in 6 (7.6 %) CRCs with MSI-H, but not in MSS/MSI-L cancers (0/65) (p < 0.025). We also analyzed intratumoral heterogeneity (ITH) of the MECOM frameshift mutation in 16 CRCs and found that four CRCs (25.0 %) harbored regional ITH of the frameshift mutations. Our data indicate that MECOM gene harbors both somatic frameshift mutations and mutational ITH, which together may be features of CRC with MSI-H.

Histone Demethylase Gene PHF2 Is Mutated in Gastric and Colorectal Cancers.

Abstract: Alterations of genes involved in histone modification are common in cancers. A histone demethylase-encoding gene PHF2 is considered a putative tumor suppressor gene (TSG). PHF2 is essential for p53-mediated TSG functions such as chemotherapy-mediated cancer cell killing. However, inactivating mutations of PHF2 that could inactivate its functions are not reported in cancers. In a genome database, we observed that the PHF2 gene possessed mononucleotide repeats, which could be mutated in cancers with high microsatellite instability (MSI-H). For this, we analyzed 124 colorectal cancers (CRCs) and 79 gastric (GCs) cancers for the mutations and their intratumoral heterogeneity (ITH). Twenty-two of 79 CRCs (27.8 %) and 7 of 34 GCs (20.6 %) harboring MSI-H exhibited frameshift mutations. However, we found no such mutations in microsatellite stable/low MSI (MSS/MSI-L) cancers. Also, we studied ITH for the detected frameshift mutations in 16 cases of CRCs and detected ITH in two (12.5 %) cases. Our data reveal that TSG gene PHF2 harbors mutational ITH as well as the frameshift mutations in CRC and GC with MSI-H. Based on this, it is suggested that frameshift mutations of PHF2 may play a role in tumorigenesis through its TSG inactivation in CRC and GC.

Frameshift Mutations of SMG7 Essential for Nonsense-Mediated mRNA Decay in Gastric and Colorectal Cancers.

Abstract: To the Editor, Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that reduces errors in gene expression by eliminating mRNA transcripts that contain premature stop codons [1]. Without the NMD, translation of such aberrant mRNAs could lead to deleterious gain-of-function or dominant-negative activity of the resulting proteins. As for tumors, suppressed NMD can either promote or inhibit tumors depending on the natures of NMD-candidate transcripts. For example, NMD shows a tumor suppressor activity in the cancers with truncated forms of BRCA1 [2]. By contrast, it shows an oncogenic role in those with truncated forms of CDH1 [3]. In humans, NMD depends on UPF1 and six other proteins SMG1, UPF2, UPF3, SMG6, SMG5 and SMG7 [1]. The SMG7 coordinates with UPF1 to degrade NMD-candidate transcripts [4]. NMDinactivating mutation of UPF1 gene is common in pancreatic adenosquamous carcinoma [5], indicating that NMD inhibition by somatic mutations of NMD machinery could possibly contribute to tumorigenesis. However, mutational status of the other genes is largely unknown. There is a mononucleotide repeat (A9) in the coding sequence of SMG7 that could be a target for frameshift mutation in cancers with microsatellite instability (MSI) such as gastric (GCs) and colorectal (CRCs) cancers [6]. To see whether SMG7 gene harbored frameshift mutations within the repeat in GC and CRC, we analyzed the A9 repeat in exon 17 of SMG7 in 34 GCs with high MSI (MSI-H), 45 GCs with microsatellite stable/low MSI (MSS/MSI-L), 79 CRCs with MSI-H and 45 CRCs with MSS/MSI-L by polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) assay as described previously [7]. Radioisotope ([P]dCTP) was incorporated into the PCR products for detection by autoradiogram. The PCR products were subsequently displayed in SSCP gels. After SSCP, Sanger DNA sequencing reactions were performed in the cancers with mobility shifts in the SSCP as described previously [8]. In the SSCP, we found aberrantly migrating bands in two GCs and six CRCs, but not in their normal samples. DNA sequencing analysis confirmed that the aberrant bands represented SMG7 somatic mutations, which consisted of frameshift mutations by a deletion (c.2454delA (p. Met849fsx1)) and a duplication (c.2545dupA (p. Met849Asnfsx10)) within the repeat (Fig. 1). The mutations were detected in GCs (2/34, 5.9 %) and CRCs (6/79, 7.6 %) with MSI-H, but not in GCs (0/45) and CRCs (0/45) with MSS/MSI-L (Fisher’s exact test, p = 0.008). Clinical and histopathological parameters, however, could not distinguish SMG7 mutation (+) and (−) cancers. Of the 79 CRCs with MSI-H analyzed, we analyzed multiregional areas in 16 CRCs (96 areas, 4–7 areas per case). One of the 16 CRCs (6.3 %) showed the deletion (c.2454delA) in two of the six regional fragments, indicating intratumoral heterogeneity (ITH) of the SMG7 frameshift mutation. We could not find any significant histological difference among the ITH regions. Earlier identification of NMD-inactivating mutation of UPF1 gene [5] led us to further analyze frameshift mutations of SMG7, another NMDmachinery gene. In the present study, we found that eight cases (7.1%) of GCs and CRCswithMSIH harbored SMG7 frameshift mutations, indicating that SMG7 gene is not uncommon in GCs and CRCs with MSI-H. The N* Sug Hyung Lee suhulee@catholic.ac.kr

Rare frameshift mutations of putative tumor suppressor genes CSMD1 and SLX4 in colorectal cancers.

Abstract: CUB and Sushi multiple domains 1 (CSMD1) is mapped to chromosome 8p23 that is frequently deleted in head and neck cancers [1]. Decreased expression of CSMD1 is also common in lung, breast, head/neck and skin cancers [2]. Structure-specific endonuclease subunit (SLX4) encodes a Fanconi anemia-related protein that is required for repair of specific types of DNA lesions and critical for cellular responses to replication fork failure [3]. SLX4 interaction with SUMO plays an important role in maintenance of genome [4], instability of which is a key feature of cancer. Together, these data suggest that both CSMD1 and SLX4 might have tumor suppressor gene (TSG) activities in cells [1,2.4]. However, it remains unknown whether inactivating frameshift mutations of their inactivating mutations are common in colorectal cancer (CRC). About 10–20% third of CRC are classified as high microsatellite instability (MSI-H) cancers [5]. Lots of TSGs harbor frameshift mutations at monocleotide repeats in MSI-H cancers [5]. In the human genome database, we observed that both CSMD1 and SLX4 genes possess nucleotide repeats in coding sequences that might be mutated in MSI-H cancers. In this study, we analyzed a T7 repeat in CSMD1 and a C7 repeat in SLX4 by polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) assay. In this study, we used 124 CRCs. The CRCs were 79 CRCs with MSI-H and 45 CRCs with microsatellite stable (MSS). In cancer tissues, malignant cells and normal cells were selectively procured by microdissection [6]. Radioisotope ([P]dCTP) was incorporated into the PCR products, which were subsequently displayed in SSCP gels and analyzed with direct DNA sequencing [6]. On SSCP, we observed aberrant bands of CSMD1 in one case of CRCs and SRPK1 in two cases of CRCs. Sanger sequencing of them revealed that they were frameshift mutations of CSMD1 and SLX4 (Fig. 1). DNA from the patients’ normal tissues showed no evidence of mutation in both SSCP and Sanger sequencing, indicating the mutations had risen somatically. These mutations were all deletions of one base in the T7 repeat of CSMD1 (c.9722delT) and the C7 repeat of SLX4 (c.140delC) that would result in frameshift mutations (p.Phe3241SerfsX21 of CSMD1 and p.Pro469HisfsX4 of SLX4) (Fig. 1). They were detected in two CRCs (3/79: 3.8%) with MSI-H, but not in those with MSS (0/45). The frameshift mutations of CSMD1 and SLX4 detected in the present study would result in premature stops of amino acid synthesis in CSMD1 and SLX4 proteins, respectively, and hence resemble a typical inactivating mutation. Based on the earlier data that showed TSG activities of PLA2R1

Candidate tumor suppressor gene MCPH1 is mutated in colorectal and gastric cancers.

Abstract: Dear Editor: Microcephalin1 (MCPH1) gene encodes a DNA damage response protein that plays a role in G2/M checkpoint arrest via maintenance of inhibitory phosphorylation of cyclindependent kinase. Also, MCPH1 is a repressor of the transcriptional activity of hTERT (the catalytic subunit of the human telomerase), indicating a potential role in cellular immortalization and tumorigenesis. It is located on the human chromosome 8p23.1, which is frequently deleted in several cancers. Also, expression of MCPH1 is decreased in several cancers, including breast and ovary cancers. Functionally, overexpression of MCPH1 inhibits cell growth and promotes cell death pathways, and knockdown of MCPH1 causes oncogenic transformation of normal epithelial cells. Together, these studies suggest that MCPH1 may possess tumor suppressor gene (TSG) activities. Approximately one third of colorectal (CRC) and gastric (GC) cancers have defects in mismatch repair that can result in microsatellite instability (MSI). Frequently, TSGs are found to harbor mutations at monocleotide repeats within the genes in high MSI (MSI-H) cancers. There is a mononucleotide repeat (A9) in the coding sequence of MCPH1 gene that could be a target for frameshift mutation in cancers with microsatellite instability (MSI) such as GC and CRC. We hypothesize that MCPH1 gene harbors frameshift mutations at the A9 repeat, which may result in inhibition of the TSG activities and contribute to tumorigenesis. To see whether MCPH1 gene harbored frameshift mutations within the repeat, we analyzed the A9 repeat of in 34 GCs with high MSI (MSI-H), 45 GCs with microsatellite stable/low MSI (MSS/MSI-L), 79 CRCs with MSI-H, and 45 CRCs with MSS/MSI-L by polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) assay. Radioisotope ([P]dCTP) was incorporated into the PCR products for detection by autoradiogram. The PCR products were subsequently displayed in SSCP gels. After SSCP, Sanger DNA sequencing reactions were performed in the cancers with mobility shifts in the SSCP. In the SSCP, we found aberrantly migrating bands in seven CRCs and four GCs, but not in their normal tissues. DNA sequencing analysis confirmed that the aberrant bands representedMCPH1 somatic mutations, which consisted of frameshift mutations by a deletion (c.321delA (p.Lys107AsnfsX39) in six CRCs and three GCs)) and a duplication (c.321dupA (p.Arg108ThrfsX2) in one CRC and one GC) within the repeat (Fig. 1). The mutations were detected in CRCs (7/79, 8.9 %) and GCs (4/34, 11.8 %) and with MSI-H, but not in GCs (0/45) and CRCs (0/45) withMSS/MSI-L (Fisher’s exact test, p = 0.001). Clinical and histopathological parameters, however, could not distinguish the MCPH1 mutation (+) and (−) cancers. Additionally, to see whether the MCPH1 mutations harbor intra-tumor heterogeneity (ITH) that is known to play a role in tumor pathogenesis, we studied 16 CRCs with four to seven regional biopsies per CRC. Two of the 16 CRCs (12.5 %) showed the deletion mutation (c.321delA), indicating there existed ITH of the MCPH1 frameshift mutation. A CRC showed the c.321delA mutation in three regions, but there was no such mutation in the other one region. Another CRC showed the c.321delAmutation in two regions, but none in the other three regions. Yun Sol Jo and Sung Soo Kim contributed equally to this work.

USP9X, a Putative Tumor Suppressor Gene, Exhibits Frameshift Mutations in Colorectal Cancers

Abstract: To the Editor: USP9X is a member of the peptidase C19 family that encodes a protein that is similar to ubiquitin-specific proteases. Two opposite activities (a tumor suppressor gene (TSG) and oncogenic) of TMEFF2 have been identified [1–4]. USP9X stabilizes MCL1 in human follicular lymphomas and diffuse large B-cell lymphomas and increases the survival of tumor cells [1]. USP9X inhibition promotes radiation-induced apoptosis in non-small cell lung cancer [2]. These data suggest oncogenic activity of USP9X in cancers. By contrast, USP9X was identified as a TSG in pancreatic ductal adenocarcinoma by ‘sleeping Beauty’ transposon-mediated insertional mutagenesis model [3]. Although previous work had attributed oncogenic roles to USP9X in human tumors [1, 2], this study found instead that loss of USP9x enhances transformation and protects pancreatic ductal adenocarcinoma cells from cell death [3]. In human cancers, low USP9X expression correlates with poor survival and treatment with 5-aza-2-primedeoxycytidine elevates USP9X expression in pancreatic ductal adenocarcinoma cell lines [3]. Also, USP9X downregulation renders breast cancer cells resistant to tamoxifen [4]. These reports [3, 4] suggest that USP9X is a TSG with prognostic and therapeutic relevance in cancers. Collectively, these studies suggest that alteration of USP9X may be tumor typedependent. However, somatic inactivating mutation status of USP9X remains undetermined in most carcinomas. There is a mononucleotide repeat (A7) in the coding sequence of USP9X that could be a target for frameshift mutation in cancers with microsatellite instability (MSI) such as colorectal cancers (CRC) [5]. To see whether USP9X gene harbored frameshift mutations within the repeat in CRC, we analyzed the A7 repeat in exon 43 in 79 CRCs with high MSI (MSI-H) and 45 microsatellite-stable/low MSI (MSS/MSI-L) CRCs by polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) assay as described previously [6]. The MSI evaluation system used five mononucleotide repeats (BAT25, BAT26, NR-21, NR-24 and MONO27), tumoral MSI status of which was characterized as: MSIH, if two or more of these markers show instability, MSI-L, if one of the markers shows instability and MSS, if none of the markers shows instability [7]. In cancer tissues, malignant cells and corresponding normal tissue were selectively procured by microdissection and their DNAs were used in the PCR [8]. Radioisotope ([P]dCTP) was incorporated into the PCR products for detection by autoradiogram. The PCR products were subsequently displayed in SSCP gels. After SSCP, Sanger DNA sequencing reactions were performed in the cancers with mobility shifts in the SSCP as described previously [6]. In the SSCP, we found aberrantly migrating bands in four CRCs with MSI-H (5.1 %) (Fig. 1), but not in their normal DNA. DNA sequencing analysis confirmed that the aberrant bands represented USP9X somatic mutations, which consisted of frameshift mutations by a deletion of one base (c.7440delA (p.Ala2481Profsx7)) and a duplication of one base (c.7440dupA (p.Ala2481Serfsx17)) within the repeat (Fig. 1). The mutations were detected in CRCs with MSIH, but not in those with MSS/MSI-L. Clinical and histopathological parameters could not distinguish USP9X mutation (+) and (−) cancers, possibly due to the small number of the mutated cases. * Sug Hyung Lee suhulee@catholic.ac.kr

Intratumoral heterogeneity for inactivating frameshift mutation of CUX1 and SIRT1 genes in gastric and colorectal cancers.

Abstract: Both CUX1 and SIRT1 are considered tumor suppressor genes (TSGs), but it is not known whether CUX1 and SIRT1 alterations are different between high microsatellite instability (MSI-H) and microsatellite stable MSI (MSS) cancers. We identified frameshift mutations of CUX1 in 4 cases of colorectal cancer (CRC) and of SIRT1 in 1 case of gastric cancer (GC) and 3 cases of CRC. All of them were found in GC or CRC with MSI-H (3.5% of MSI-H for each gene), but neither in GC nor CRC with MSS. In addition, we analyzed intratumoral heterogeneity (ITH) of the CUX1 frameshift mutation and found that two CRCs (12.5%) harbored regional ITH of the frameshift mutation. Our data indicate that there exist frameshift mutations of CUX1 and SIRT1 genes as well as ITH of CUX1 frameshift mutation in MSI-H cancers, which together might play a role in tumorigenesis of GC and CRC with MSI-H.

WRN, the Werner Syndrome Gene, Exhibits Frameshift Mutations in Gastric and Colorectal Cancers

Abstract: To the Editor Werner syndrome, an autosomal recessive disorder causing premature aging, is caused by truncating mutations in Werner syndrome gene (WRN) that encodes a DNA helicase with exonuclease activity [1]. Patients with Werner syndrome have an increased cancer incidence as well, suggesting that the lack normal WRN function affects tumorigenesis [2]. Both helicase and exonuclease activities ofWRN protein contribute to DNA repair in cells [3]. Also, cells with defective WRN show genomic instability [4]. These features are frequently observed in cancers, suggesting a possibility of WRN gene alterations in cancers. However, it remains unknown whether inactivating mutation of WRN is common in gastric cancer (GC) and colorectal cancer (CRC). About one third of GC and CRC are classified as high microsatellite instability (MSI-H) cancers [5]. Many tumor suppressor genes such as BAX and TGFBR2 harbor frameshift mutations at monocleotide repeats in MSI-H cancers [5]. In the human genome database, we observed that WRN gene possesses nucleotide repeats in coding sequences that might be mutated in MSI-H cancers. In this study, we analyzed an A8 repeat in exon 2 and an A7 repeat in exon 28 of WRN by polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) assay. In this study, we used 79 GCs and 124 CRCs. The GCs were 34 GCs with MSI-H, 45 GCs with microsatellite stable/low MSI (MSS/ MSI-L), 79 CRCs with MSI-H and 45 CRCs with MSS/ MSI-L. In cancer tissues, malignant cells and normal cells were selectively procured by microdissection. Radioisotope ([P]dCTP) was incorporated into the PCR products, which were subsequently displayed in SSCP gels and analyzed with direct DNA sequencing [6]. Additionally, to see whether the WRN mutations possess intra-tumor heterogeneity (ITH) that contributes to tumor aggressiveness [7], we studied 16 CRCs with four to seven regional biopsies per CRC. In the SSCP, we found aberrantly migrating bands in three GCs and three CRCs, but not in their matched normal samples. DNA sequencing analysis confirmed that the aberrant bands represented WRN somatic mutations, which consisted of frameshift mutations by a deletion (c.15delA (p. Lys5AsnfsX15)) in exon 2 and another deletion (c.3382delA (p. Ser1128ValfsX34)) in exon 28 within the repeat (Table 1). The mutations were found in GCs (3/34, 8.8%) and CRCs (3/79, 3.8%) with MSI-H (3/113, 5.3%), but not in GCs (0/45) and CRCs (0/45) with MSS/MSI-L (Fisher’s exact test, p = 0.028). The frameshift mutation in exon 2 showed ITH in one of 16 CRCs (6.3%). A CRC (# 41) showed the c.15delA mutation in three regional biopsies (#41–1, 41–3 and 41–4), but there was no such mutation in the two regional biopsies (#41–6 and 41–7) (Fig. 1). We could not find any significant histological difference among the ITH regions in this case. Cancer-related functions (DNA repair and maintenance of genomic stability) and increased cancer incidence in Werner syndrome [1] led to us to analyze inactivating mutations of WRN gene in GC and CRC. In the present study, we found that six cases (5.3%) of GCs and CRCs with MSI-H harbored WRN frameshift mutations, indicating that WRN is mutated Ju Hwa Lee and Sung Soo Kim contributed equally to this work.

Frameshift Mutation of FXR1 Encoding a RNA-Binding Protein in Gastric and Colorectal Cancers with Microsatellite Instability.

Abstract: To the Editor: Fragile X mental retardation syndrome-related protein 1 (FXR1) gene encodes an RNA binding protein that is a critical regulator of post-transcriptional gene expression in differentiation, development and immunity [1]. Because FXR1 coordinates networks of RNA–protein and protein–protein interactions that link RNA metabolism to signal transduction pathways, altered function of FXR1 is expected to contribute to development of human diseases including cancer [1]. For example, association of FXR1 with RNA-protein complex (a target-specific miRNA and AGO2) is important in regulation of the post-transcriptional gene expression [2]. FXR1 resides on chromosome 3q26–29 which is frequently amplified in many cancers [1]. Elevated FXR1 expression is observed in several cancers, including colon and lung cancers and is associated with poor outcome of the patients [3]. Functionally, overexpression of FXR1 is critical for cell growth, migration and invasion, indicating that FXR1 possesses oncogenic activities (Table 1). Microsatellite instability (MSI) is the condition of impaired DNA mismatch repair (MMR) that results in deletion or insertion of bases in monoor dinucleotide repeats. MSI phenotype is most common in colorectal (CRC) and gastric (GC) cancers [4]. There is a mononucleotide repeat (A8) in the FXR1 coding sequence that could be a target for frameshift mutation in cancers with MSI. To find whether FXR1 gene harbored frameshift mutation within the repeat, we analyzed the A8 repeat of in 34 GCs with high MSI (MSI-H), 45 GCs with microsatellite stable/low MSI (MSS/MSI-L), 79 CRCs with MSI-H and 45 CRCs with MSS/MSI-L by polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) assay. Radioisotope ([P]dCTP) was incorporated into the PCR products for detection by autoradiogram. The PCR products were subsequently displayed in SSCP gels. After SSCP, Sanger DNA sequencing reactions were performed in the cancers with mobility shifts in the SSCP [5]. In the SSCP, we found aberrantly migrating bands in 14 CRCs and four GCs, but not in their normal tissues. DNA sequencing analysis confirmed that the aberrant bands represented FXR1 somatic mutation that was a deletion (c.116delA (p. Asn391IlefsX14)) within the repeat. The mutation was detected in CRCs (14/79, 17.7%) and GCs (4/34, 11.8%) with MSI-H, but not in GCs (0/45) and CRCs (0/45) with MSS/ MSI-L (Fisher’s exact test, p = 0.001). Clinical and histopathological parameters, however, could not distinguish the FXR1 mutation (+) and (−) cancers. In addition, to find whether the FXR1 mutation harbor intra-tumor heterogeneity (ITH) that is known to play a role in evolution as well as treatment resistance in cancers, we studied 16 cases of CRCs with four to seven regional biopsies per CRC. Three of the 16 CRCs (18.8%) showed the deletion mutation (c.116delA) in different tissue regions, indicating ITH of the FXR1 mutation existed in CRC. Yun Sol Jo and Sung Soo Kim contributed equally to this work.

Mutational analysis of H3F3B gene in acute leukaemias and solid tumours.

Abstract: dulthood AML 206 206 0 (0) dulthood ALL 156 156 0 (0) hildhood AML 21 21 0 (0) hildhood ALL 201 200 1 (0.5) ultiple myeloma 75 75 0 (0) yelodysplasia 68 68 0 (0) on-Hodgkin lymphoma 105 105 0 (0) on-small cell lung cancer 208 208 0 (0) astric carcinoma 201 201 0 (0) olorectal carcinoma 417 414 3 (0.7) reast carcinoma 81 81 0 (0) rostate carcinoma 263 263 0 (0) varian epithelial tumours 15 15 0 (0) varian granulosa cell tumours 69 68 1 (1.5) epatocellular carcinomas 36 36 0 (0) epatoblastomas 20 20 0 (0) sophageal squamous cell carcinomas 61 61 0 (0) aryngeal squamous cell carcinomas 44 45 0 (0) eiomyoma 68 68 0 (0) astrointestinal stromal tumours 20 20 0 (0) alignant peripheral nerve sheath mour 22 21 1 (4.5)