title: 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.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, South Korea.
authors.forename: Joo Hwa
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, South Korea.
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, South Korea.
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Kim
authors.affiliation: 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.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
mesh_terms: D063646:Carcinogenesis / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics*; D056466:Histone Demethylases / Q000235:genetics*; D006657:Histones / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D006657:Histones; D018398:Homeodomain Proteins; C117905:PHF2 protein, human; D056466:Histone Demethylases
keywords: Cancer; Frameshift mutation; Intratumoral heterogeneity; Microsatellite instability; PHF2; Tumor suppressor gene