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Mutation of KRAS genes occurs with a frequency of 0.5-32 % in AML. In the present study, mutations of KRAS codon 12, 13, and 61 were detected by pyrosequencing and direct sequencing in AML. Seven KRAS mutations (7/123, 5.7 %) were detected. The most common mutation was a G-to-A transition in the second base of KRAS codon 13. No mutations were detected in KRAS codon 61. Combinations of KRAS and FLT3 mutation were not found in the same patient. There was no statistically significant difference between patients with KRAS mutations and patients with wild-type KRAS in terms of sex, age, CBC at diagnosis, CD34 positivity, MPO positivity, FLT3 mutation, karyotype, progression-free survival, and overall survival, although this may be attributable to the small sample size. To our knowledge, this is the first report of the detection of KRAS mutation in Asian AML patients using pyrosequencing and direct sequencing. These two methods showed identical efficiencies in their ability to detect KRAS mutations in 84 patients.

We evaluated p53, KRAS, BRAF and CTNNB1 mutation and p53, WT1, p16 and beta-catenin expression in 31 ovarian high-grade serous adenocarcinoma. Twenty-five (80.6%) tumors contained functional mutations of p53; three frameshift, four nonsense and 19 missense mutations. None of the tumors showed KRAS, BRAF or CTNNB1 mutation. In all 18 tumors with missense mutations, ≥60% of tumor cells were strongly positive for p53 immunostaining whereas all tumors with frameshift or nonsense mutations were completely negative. Missense mutation was correlated with diffuse and strong imunoreaction and frameshift/nonsense mutation was correlated with completely negative immunoreaction (P = 0.000). Tumors with wild-type p53 revealed a wide range of immunostaining patterns. In 27 (87.1%) and 18 (58.1%) tumors, ≥50% of tumor cells were moderate to strongly positive for WT1 and p16, respectively. A considerable intratumoral heterogeneity for p16 expression was present. None of the tumors demonstrated nuclear beta-catenin expression. p53 mutations appear to be a powerful molecular marker for ovarian high-grade serous adenocarcinoma. Using p53 with an appropriate interpretation criteria together with WT1, p16 and beta-catenin, most of the high-grade serous adenocarcinoma could be distinguished from other ovarian tumors., (© 2013 The Authors. Pathology International © 2013 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.)

Mucosal and acral melanomas have demonstrated different genetic alterations and biological behavior compared with more common cutaneous melanomas. It was recently reported that gain-of-function KIT mutations and/or copy number increases are more common in mucosal and acral melanomas. Thus, we studied the frequency and pattern of KIT aberrations in mucosal and acral melanomas in Korea. We analyzed 97 patients who were pathologically confirmed with mucosal or acral melanoma between 1997 and 2010 at Samsung Medical Center. Of the 97 melanoma patients, 92 were screened for mutations in KIT exons 11, 13, 17, and 18, BRAF and NRAS genes. KIT copy number was assessed by quantitative, real-time PCR. Of the 97 patients, 55 (56.7%) were mucosal, 40 (41.2%) were acral melanoma, and two were of unknown primary origin. Among seven cases with KIT mutation, five (60.0%) occurred in exon 11, one (20.0%) in exon 17, and one (20.0%) in exon 13. Point mutations were the most common, resulting in substitutions in exon 11 (K558R, T574A, L576P, and V559A), exon 13 (N655K), and exon 17 (N822K). A novel Thr574Ala (c.1720A>G) KIT mutation, which has not been reported in melanoma or other tumor types, was identified in one genital melanoma case. Of the 97 mucosal or acral melanoma specimens, 49 were tested for KIT gene copy number changes using quantitative PCR. Increased KIT copy number was identified in 15 patients: seven (40%) of 20 acral melanomas and eight (31%) of 26 mucosal melanomas. Our study implicates that a significant proportion of acral and mucosal melanomas have KIT mutations in Asian population., (© 2011 The Authors. APMIS © 2011 APMIS.)