Showing papers by "Nam Jin Yoo published in 2008"

Somatic Mutations of JAK1 and JAK3 in Acute Leukemias and Solid Cancers

Abstract: Purpose: The aim of this study was to see whether JAK1, JAK3 , and TYK2 genes are altered in human cancers. Experimental Design: We analyzed 494 tissues from 186 acute adulthood leukemias, 30 multiple myelomas, and 278 common solid cancers, including 90 breast, 47 gastric, 47 colon, 47 lung, and 47 hepatocellular carcinomas by single-strand conformation polymorphism analysis. Results: Overall, we found six JAK1 mutations (four in acute leukemias, one in a lung carcinoma, and one in a breast carcinoma) and three JAK3 mutations (two in breast carcinomas and one in a gastric carcinoma). Of note, three JAK1 mutations were an identical p.V658F mutation, which is homologous to JAK2 p.V617F mutation. We also found two other JAK1 mutations that occurred at very close sites (p.T782M and p.L783F). We found three of the four leukemias with JAK1 mutations expressed mutated JAK1 at the mRNA level. For JAK3 mutations, one of them was JAK3 p.V715I that is homologous to the JAK1 p.L783F. These recurrent mutations in identical and homologous sites suggest a possibility that alterations of these amino acids might be important for tumor pathogenesis. With respect to the cancer types, T-acute lymphoblastic leukemia (T-ALL) showed the highest incidence of the mutations (3 of 11; 27.3%). Conclusion: Our data indicate that both JAK1 and JAK3 mutations occur in common human cancers and that JAK1 mutation in T-ALL is a frequent event. The data suggest that some of the JAK1 and JAK3 mutations may to be functional and contributes to cancer development, especially to T-ALL development.

Expression of NEDD‐1, a PTEN regulator, in gastric and colorectal carcinomas

Abstract: Recent studies have disclosed that NEDD4-1 regulates PTEN activity by ubiquitination. NEDD4-1 negatively regulates PTEN in cytosol and acts as an oncogenic protein. By contrast, NEDD4-1 promotes PTEN nuclear import and acts as a tumor suppressor. Despite the importance of NEDD4-1 in PTEN regulation in cancer cells, expression of NEDD4-1 protein in cancer tissues is unknown. The aim of this study was to analyze NEDD4-1 expression in colorectal and gastric cancer tissues. We investigated NEDD4-1 protein expression in 103 colorectal and 60 gastric carcinoma tissues by immunohistochemistry using a tissue microarray approach. In the cancers, expression of NEDD4-1 was detected in 82 (80%) of the colorectal carcinomas and 45 (75%) of the gastric carcinomas in cytoplasm. By contrast, the normal mucosal cells of both stomach and colon showed no or very weak expression of NEDD4-1. There was no significant association of NEDD4-1 expression with clinicopathologic characteristics, including invasion, metastasis and stage. Our data indicate that NEDD4-1 overexpression is a feature of both colorectal and gastric carcinomas. The increased expression of NEDD4-1 in malignant gastric and colorectal cells compared to their normal epithelial cells suggests that NEDD4-1 expression may play a role in colorectal and gastric cancer development.

Absence of COSMC gene mutations in breast and colorectal carcinomas

Abstract: Cancer patients have serum antibodies that are reactive to their cancer cells, but not to normal cells. However, the nature of these cancer-specific epitopes is largely unknown. Many cancerspecific proteins resulting from somatic mutation reside in the intracellular space and cannot be accessible to antibodies. There are a few cancer-specific antigens on the cancer cell surface created by somatic mutations that could be potential targets for cancer immunotherapy (1). Tn antigen (also known as GalNAca1-Ser/ Thr) is a precursor of longer O-glycans such as core 1 (2). For the maturation of Tn antigen to core 1, C1b3Gal-T activity is required. Core 1b3Gal-T-specific molecular chaperone (COSMC; also known as C1GALT1C1) is a molecular chaperone that is required for C1b3Gal-T activity (3). Without COSMC, the C1b3Gal-T is targeted to the proteosome and degraded (3). The Tn antigen is overexpressed in many cancers, including colorectal and breast cancers (4, 5). Recent studies revealed that cancer-specific mutations in the COSMC gene remove C1b3Gal-T activity, disrupt O-glycan core 1 synthesis, lead to Tn antigen overexpression, and create a cancerspecific epitope on the cell surface (2, 3, 6). Somatic mutations of the COSMC gene have been found in both mouse (Ag104A fibrosarcoma and Neuro2A neuroblastoma) and human (Jurkat Tcell leukemia and LSC colorectal cancer) cancer cell lines (2, 3, 6). The COSMC mutations consisted of insertion of a T nucleotide (LSC), deletion of a T nucleotide (Jurkat), deletion of 78 nucleotides (Ag104A) and non-sense substitution of a nucleotide (Neuro2A). These mutations would result in premature stops of amino acid synthesis or deletion of a large portion of the

Expressional and mutational analysis of pro-apoptotic Bcl-2 member PUMA in hepatocellular carcinomas.

Abstract: Deregulation of apoptosis is involved in mechanisms of cancer development. PUMA is a pro-apoptotic member of the Bcl-2 family and mediates p53-dependent and -independent apoptosis. The aim of this study was to investigate whether alterations of PUMA protein expression and somatic mutations of PUMA gene are characteristics of human hepatocellular carcinoma (HCC). We analyzed expression of PUMA protein in 20 HCCs using immunohistochemistry. Also, we analyzed mutation of the Bcl-2 homology 3 (BH3) domain of PUMA gene, which is an important domain in apoptosis function of PUMA by single-strand conformation polymorphism (SSCP) in 69 HCCs. PUMA protein expression was detected in both HCC cells and non-tumor hepatocytes in all of the 20 HCCs. In 10 of these HCCs, cancer cells showed higher PUMA expression than non-tumor (cirrhotic) hepatocytes of the same patients; whereas in the remaining 10, cancer cells and non-tumor hepatocytes showed similar levels. Mutational analysis revealed no PUMA BH3 domain mutation in the 69 HCCs, suggesting that PUMA BH3 domain mutation is not a direct target of inactivation in hepatocellular cancer development. The increased expression of PUMA in malignant hepatocellular cells relative to that in non-tumor hepatocytes suggests that PUMA expression may play a role in HCC development.

Tumor suppressor WTX gene mutation is rare in acute leukemias.

Abstract: Recently, Rivera et al. [1] found genetic alterations of an X chromosome gene, Wilms' tumor gene on the X chromosome (WTX) gene in sporadic Wilms' tumors. They detected small deletions and point mu...

Absence of JAK2 exon 12 mutation in acute leukemias.

Abstract: kemias [AMLs with t(q22;q12)], 11 AMLs with multilineage dysplasia, and 1 AML and myelodysplastic syndrome, therapy related according to WHO classification. The acute leukemia DNA samples were extracted from bone marrows of 142 acute leukemia patients (age range 20–80 years). We also analyzed bone marrow DNAs from 11 PV patients that consisted of five V617F-positive and six V617F-negative cases. All patients were Asians (Korean). Approval was obtained from the Catholic University of Korea, College of Medicine’s institutional review board for this study. Genomic DNA was isolated and analyzed for potential mutations in the JAK2 exon 12 by polymerase chain reaction (PCR) with one primer pair (5 -AGTGTATTTTGAAGTGAT-3 and 5 -AAAAGACAGTAATGAGTATC-3 ). Radioisotope ([ 32 P]dCTP) was incorporated into PCR products for detection by autoradiogram. The PCR products were subsequently analyzed by a single-strand conformation polymorphism (SSCP) analysis as described previously [4] . On SSCP autoradiogram, all PCR products were clearly seen. However, the SSCP from the acute leukemia samples did not reveal any aberrantly migrating bands compared to wild-type bands from normal tissues of the same patients, indicating there was no evidence of JAK2 exon 12 mutation in the acute leukemia samples. By contrast, we detected a JAK2 exon 12 mutation in 2 unrelated PV samples ( fig. 1 ). This mutation was N542-E453del, which was previously reported in PV bone marrows [3] . This Recently, several research groups reported a somatic missense mutation in exon 14 of JAK2 gene (V617F) in myeloproliferative disorders (MPD), including polycythemia vera (PV) [1] . In addition to the JAK2 V617F mutation, Scott et al. [2] recently found additional JAK2 mutations in exon 12 (F537-K539delinsL, N542-E543del, K539L and H538Q), which were detected in V617F-negative PV and V617F-negative idiopathic erythropoiesis. By contrast, they were not detected in V617F-positive PV, V617F-negative essential thrombocythemia or V617Fnegative myelofibrosis with myeloid metaplasia, either [2, 3] . Functionally, hematopoietic cells bearing the JAK2 exon 12 mutations were able to proliferate in the absence of added exogenous cytokine and had activated erythropoietin signaling [2] . To see whether the JAK 2 exon 12 is also mutated in acute leukemias as well, we randomly selected 142 acute leukemias and analyzed the JAK2 exon 12 mutation in the leukemias. The acute leukemias consisted of 105 acute myeloid leukemias (AMLs), 36 acute lymphoblastic leukemias (ALLs; 32 B-ALLs and 4 T-ALLs) and 1 undifferentiated acute leukemia. The AML samples consisted of 8 minimally differentiated AMLs, 15 AMLs without maturation, 21 AMLs with maturation, 7 acute myelomonocytic leukemias, 7 acute monoblastic and monocytic leukemias, 2 acute erythroid leukemias, 15 AMLs with t(8; 21)(q22;q22), 6 AMLs with abnormal bone marrow eosinophils Inv(16)(p13q22), 12 acute promyelocytic leuReceived: July 17, 2007 Accepted after revision: September 13, 2007 Published online: January 30, 2008

Somatic mutation of pro-cell death Bif-1 gene is rare in common human cancers.

Abstract: Failure of cell death could allow the survival of transformed cells that are prone to undergo further genetic damage and play an important role in the pathogenesis of cancers. Bax-interacting factor-1 (Bif-1) interacts with both Bax and Bak, which are essential for the intrinsic pathway of apoptosis, and enhances apoptosis (1). Also, Bif-1 interacts with Beclin-1 through the UV radiation resistance-associated gene (UVRAG) and induces autophagic cell death (2). Functionally, suppression of Bif-1 expression was associated with enhanced ability of cells to form colonies in soft agar and tumors in nude mice (1), suggesting inactivation of Bif1 may contribute to tumorigenesis. Somatic mutations of cell death-related genes have been reported in human cancers, and many of the mutations were proven to inactivate cell death (3, 4). Because Bif-1 is an important mediator of cell death, it is possible that alteration of the Bif-1 gene could be responsible for the pathogenesis of human cancers. The aim of this study was to identify somatic mutations of the Bif-1 gene in cancer tissues. For this, methacarn-fixed tissues of 48 lung, 48 gastric, 47 hepatocellular, 47 colorectal and 47 breast carcinomas, and 47 acute adulthood leukemias from Koreans were randomly selected. The lung carcinomas consisted of 20 squamous cell carcinomas, 20 adenocarcinomas, and 8 large cell carcinomas. The colorectal carcinomas originated from cecum (NΩ2), ascending colon (NΩ8), transverse colon (NΩ2), descending colon (NΩ3), sigmoid colon (NΩ11) and rectum (NΩ21). The gastric carcinomas consisted of 19 diffuse-type, 15 intestinal-type and 14 mixed-type advanced gastric adenocarcinomas. The breast carcinomas consisted of 5

Increased expression of endonuclease G in gastric and colorectal carcinomas.

Abstract: Aims. Endonuclease G (EndoG) is a mitochondrial protein that plays a role in DNA fragmentation during apoptosis. In addition, EndoG plays a role in cell proliferation and survival. It may be important to identify EndoG protein expression to predict its function in human cancers. The aim of this study was to explore whether alteration of EndoG expression might be a characteristic of colorectal or gastric carcinoma. Methods. We investigated EndoG protein expression in 103 colorectal and 60 gastric carcinoma tissues by immunohistochemistry using a tissue microarray approach. Results. Expression of EndoG was detected in 72 (70%) of the colorectal carcinomas and 41 (68%) of the gastric carcinomas in cytoplasm. By contrast, normal mucosal cells of both stomach and colon tissues showed no or very weak expression of EndoG. There was no significant association of EndoG expression with clinocopathological characteristics, including invasion, metastasis and stage. Conclusion. Our data indicate that EndoG inactivation by loss of expression may not occur in colorectal and gastric cancers. Rather, increased expression of EndoG in colorectal and gastric cancer cells compared to their normal mucosal epithelial counterparts suggests that neo-expression of EndoG may play a role in both colorectal and gastric tumorigenesis.

Absence of somatic mutation of a tumor suppressor gene eukaryotic translation elongation factor 1, epsilon-1 (EEF1E1), in common human cancers

Abstract: Eukaryotic translation elongation factor 1, epsilon-1 (EEF1E1), also known as elongation factor p18 or AIMP3, is a protein associated with a tRNA synthetase complex (1). Unexpectedly, EEF1E1 was identified as a tumor suppressor (2, 3). EEF1E1 upregulates p53 by activating ATM/ ATR in response to DNA damage (2). EEF1E1 is essential for oncogene-induced p53 activation and plays an important role in preventing cellular transformation by oncogenic stresses (3). Experimentally, EEF1E1π/a mutant mice suffer from a high incidence of tumors, including breast, lung and liver carcinomas, and lymphomas, suggesting that EEF1E1 may be a haploinsufficient tumor suppressor (2). Although EEF1E1 is considered a tumor suppressor gene, data on somatic mutation of EEF1E1 that could be an inactivating mechanism of EEF1E1 function are lacking in human cancer tissues. To see whether EEF1E1 is somatically mutated in human cancers, we analyzed somatic mutations of EEF1E1 in tissue samples from gastric, colorectal, breast, hepatocellular carcinomas, acute leukemias and nonsmall cell lung cancers (NSCLC) by polymerase chain reaction (PCR)-based single-strand conformation polymorphism (SSCP) analysis in this study. For this, we analyzed the EEF1E1 gene in methacarn-fixed tissues of 47 gastric adenocarcinomas, 47 colorectal adenocarcinomas, 47 breast invasive ductal carcinomas, 47 hepatocellular carcinomas and 47 non-small cell lung cancers (NSCLC), and fresh non-fixed tissues of 47 acute myelogenous leukemias (40 acute myelogenous leukemias and 7 acute lymphoblastic leukemias) by polymerase chain reaction (PCR)

Decreased expression of endonuclease G (EndoG), a pro-apoptotic protein, in hepatocellular carcinomas

Abstract: Many molecules are involved in DNA fragmentation during apoptosis, but there are two major apoptotic nucleases, termed caspase-activated DNAse (CAD) and endonuclease G (EndoG) (1). EndoG is a nuclease located in mitochondria yet it translocates into the nucleus of apoptotic cells (1). EndoG in the nucleus cleaves chromatin DNA into nucleosomal fragments and participates in the apoptotic process (1–5). Experimentally, blockade of EndoG expression by SiRNA protects cells from apoptosis conditions (6). Substantial evidence indicates that alterations in the control of apoptosis contribute to the pathogenesis of many human diseases, including cancer (7). Failure of apoptosis could allow survival of transformed cells that are prone to suffer further genetic damage and play an important role in the pathogenesis of cancers. Hepatocellular carcinoma (HCC) cells are frequently resistant to various apoptosis stimuli (8). However, the exact mechanisms of apoptosis resistance in HCC cells are largely unknown. EndoG is expressed in mouse and rat hepatocytes where apoptosis stimuli translocate EndoG from mitochondria to nuclei and induce apoptosis (3, 9). Also, Hep3B, a HCC cell line, expresses EndoG, which has a cell death activity in the cells (10). Meanwhile, at the human tissue level, EndoG expression is unknown in both HCC and normal hepatocytes. Because EndoG plays important roles in the apoptosis of cells, it can be hypothesized that EndoG function might be altered by aberrant expression in human HCCs. In the present study, we analyzed EndoG expression in HCC, cirrhosis and normal liver tissues by immunohistochemistry, and found EndoG expression is frequently lost in HCCs.

Absence of ERCC6 gene mutation in common cancers of Korean patients

Abstract: One of the central aims of cancer research is to identify functional cancer-specific mutations that are causally implicated in tumorigenesis. Recently, Sjöblom et al. analyzed 13,023 genes (approximately one half of all human genes), a set of protein-coding genes termed the consensus coding sequences (1). In 35 breast and 35 colorectal cancer tissues, they identified 189 genes that were mutated at significant frequencies. In addition to genes that had been reported to be mutated in colorectal or breast cancers, including TP53, APC and KRAS, many other genes were newly found to be mutated in the cancers (1). Of the genes with mutations, excision-repair cross-complementing, group 6 (ERCC6) was found to be frequently mutated in breast carcinomas (3/35; 8.6%) and colorectal carcinomas (2/35; 5.7%) (1). The ERCC6 gene is involved in the nucleotide excision repair pathway that eliminates a broad spectrum of structural DNA lesions, including ultraviolet (UV)-induced cyclobutane pyrimidine dimers, bulky chemical adducts, and DNA cross-links (2). ERCC6 consisted of 21 exons that encode a 1493-amino acid protein. Germline mutations of ERCC6 have been reported in Cockayne’s syndrome, which is a multisystem sun-sensitive genetic disorder associated with a specific defect in the ability to perform transcription-coupled repair of active genes after UV irradiation (3). Defects of nucleotide repair pathways are a feature of cancer cells. However, mutations of ERCC6 have not been reported in human cancers, except for in the study of Sjöblom et al. (1). The aim of this study was to confirm the presence of ERCC6 gene mutations in colorectal and breast carcinomas, and to see whether ERCC6 mutations also occur in other types of cancers.

Absence of JAK1 exon 10 and 13 mutations in acute leukemias and multiple myelomas.

Abstract: To the Editor: Janus kinases (JAK) play important roles in normal hematopoiesis. Also, mounting evidence indicates that deregulations of JAKs are important in hematopoietic tumor development (1). Fusion of JAK2 and TEL genes to generate TEL-JAK2 kinase has been detected in patients with acute lymphoblastic leukemias (ALL) (1). JAK2 p.V617F mutation is an important underlying mechanism of polycythemia vera development (1). Recently, two types of somatic mutations of JAK1 (p.T478S in exon 10 and p.V623A in exon 13) have been reported in bone marrows of acute myelogenous leukemia (AML) patients (2). These JAK1 mutations were associated with activation of STAT signaling in response to type I interferon (2). As JAK1 signaling is important in both myeloidand lymphoid-lineage development (1), it could be hypothesized that the JAK1 mutations in exon 10 and 13 might occur in other types of leukemias besides AML. To see whether exon 10 and 13 of JAK1 are somatically mutated in acute leukemias and multiple myelomas (MM), we analyzed the mutations in 106 AMLs, 74 ALLs (60 B-ALL and 14 T-ALL) and 31 MMs. The leukemia and MM DNAs were extracted from bone marrows of the patients (age range 20–80). All of the patients were Korean. Approval was obtained from the Catholic University of Korea, College of Medicine’s institutional review board for this study. JAK1 p.T478S and the JAK1 p.V623A mutations have been detected within exon 10 and exon 13, respectively (2). To detect somatic mutations in these exons, genomic DNAs each from tumor cells and normal cells were amplified with two primer pairs covering the exon 10 and the exon 13. Radioisotope ((P)dCTP) was incorporated into the polymerase chain reaction (PCR) products for the detection by single-strand conformation polymorphism (SSCP) autoradiogram.as described previously (3). On SSCP autoradiogram, all of the PCR products were clearly seen. However, the SSCP from the acute leukemias and MM did not reveal any aberrantly migrating band compared to the wild-type bands from normal tissues, indicating there was no evidence of JAK1 exon 10 nor exon 13 mutation in the cancer specimens. We repeated the experiments twice, including PCR and SSCP, and found that the data was consistent. In leukemia pathogenesis, activation of cytokine signaling is crucial (1). As JAK1 transmits and activates cytokine signaling pathways (1), activating mutations of JAK1 gene could be an important mechanism of leukemogenesis. Based on an earlier report on activating JAK1 mutations in AMLs (2), we expected to detect some somatic mutations of JAK1 exon 10 and 13 in our set of AML specimens. However, we detected no somatic mutation of JAK1 in the exon 10 and 13. Statistically, there is no significant difference in the JAK1 mutation frequencies between the previous study (2) and our study (Fisher’s exact test, P = 0.22), suggesting that a racial difference between the two studies does not exist. In addition, neither ALL nor MM harbored the JAK1 mutations. Recently, Tomasson et al. (4) analyzed JAK1, JAK2, JAK3 and TYK2 genes simultaneously in AMLs and found no additional somatic mutations of JAK genes, indicating somatic mutations of JAK genes are rare in AML. In a recent study, Flex et al. (5) found frequent somatic mutations of JAK1 in T-ALL and B-ALL, most of which were detected outside of exon 10 and 13. Also, our recent study showed that T-ALL harbored JAK1 mutation in exon 14 and 17 (6). The data presented here and these two documents suggest that JAK1 mutations may be common in ALL, but their incidence in exon 10 and 13 may be low in ALL. As for MM, mutational analysis of the entire coding sequences of JAK1 has not been performed yet, and the incidence of JAK1 mutation outside of exon 10 and 13 remains unknown.

Somatic mutation of TRAF3 gene is rare in common human cancers and acute leukemias

Abstract: cell lymphomas with immunophenotype similar to mantle cell lymphoma but negative for Cyclin D1 and t(11;14) are best classified as CD5 B-cell chronic lymphoproliferative disorders (B-CLPD) or atypical chronic lymphocytic leukemia (aCLL). A French study [2] segregated CD5-positive, Cyclin D1-negative B-CLPD into 2 groups based on the intensity of CD20. Patients with dim CD20 profile represent a homogeneous subgroup very close to the B-CLL on morphologic, immunophenotypic and cytogenetic criteria. In contrast, they found the group expressing bright CD20 to be heterogeneous with a more aggressive course and non CLL like profile. Our patient’s lymphoma demonstrated bright CD20 and no typical cytogenetic abnormalities for CLL. The presence of bone marrow and peripheral blood involvement just a year after initial presentation (leukemic phase) demonstrates the aggressiveness of his disease. This aggressive nature may also be attributed to the atypical co-expression of CD10 by the lymphoma [3]. This case demonstrates that further studies are required to properly classify and determine prognosis of CD5 non mantle cell, non CLL B-CLPD’s and that provisions should be made in the WHO classification to accommodate these aberrant cases. Although a causal relationship between B-cell lymphoma and Hepatitis B virus has not been described to date, the possibility of chronic HBV infection as a trigger for monoclonal B-cell proliferation due to chronic antigenic stimulation may not be entirely speculative.

Alterations of the Apoptosis Genes and Their Products in Non-small Cell Lung Cancer Tissues

Abstract: Apoptosis is a principal type of cell death, and it has a profound effect on the development of cancer. It is also well known that anti-cancer agents induce apoptosis, and defects in the apoptosis pathways reduce the treatment sensitivity. Of the many pathways that induce apoptosis, the mechanisms of the intrinsic and extrinsic apoptosis pathways are well established. Non-small cell lung cancer (NSCLC) is a leading cause of cancer death worldwide, yet the exact molecular mechanisms of its development remain unclear. Apoptosis deregulations may underlie the development and pathogenesis of NSCLC. This review discusses the general mechanisms of apoptosis, the constituents of the apoptosis machinery and the alterations of the apoptosis-related genes in NSCLC. (J Lung Cancer 2008;7(2):59�� 64)

Mutational Analysis of the Tumor Suppressor WTX Gene in Non-small Cell Lung Cancer

Abstract: Purpose: In a recent study of Wilms' tumors, a new X chromosome gene, Wilms' tumor gene on the X chromosome (WTX), was discovered that was found to harbor small deletions and point mutations. The WTX protein negatively regulates Wnt/ β-catenin signaling, and is considered to be a tumor suppressor gene. One of the questions about the WTX gene is whether the genetic alterations of the WTX gene are specific only to Wilms' tumors. The aim of this study was to explore whether the WTX gene mutation is a characteristic of human non-small cell lung cancer (NSCLC). Materials and Methods: In the current study, we analyzed the part of the WTX gene encoding the N-terminal of WTX, where most of the WTX point mutations have been detected in Wilms' tumors. Forty-eight NSCLC tissues were analyzed by a single-strand conformation polymorphism assay and DNA sequencing. Results: SSCP analysis revealed no evidence of somatic mutations in the DNA sequences encoding the N-terminal of the WTX gene in the 48 NSCLC tissues. Conclusion: The data presented here indicate that the WTX gene may not be somatically-mutated in human NSCLCs, and suggest that NSCLCs may not utilize mutational events of the WTX gene in the process of pathogenesis. (J Lung Cancer 2008;7(1):22�� 24)

Mutational Analysis of JAK1 Exons 10 and 13 in Non-small Cell Lung Cancers

Abstract: Purpose: JAK kinases play important roles not only in normal cellular processes, but they are also important in tumor development. A recent study identified two somatic mutations of JAK1 in leukemia cells that were detected in exon 10 (p.T478S) and exon 13 (p.V623A). The aim of this study was to see whether the JAK1 mutations in these exons occur in non-small cell lung cancers (NSCLC). Materials and Methods: We analyzed the exons 10 and 13 of JAK1 for detecting somatic mutations in NSCLC by performing polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) assay. Results: The SSCP analysis revealed no evidence of somatic mutation in the DNA sequences of JAK1 exon 10 and exon 13 in the 47 NSCLCs. Conclusion: The data presented here indicate that the JAK1 exons 10 and 13 may not be somatically mutated in human NSCLCs, and this suggests that the JAK1 mutation in exons 10 and 13 may not play an important role in the tumorigenesis of NSCLCs. (J Lung Cancer 2008;7(2):71 �� 74)