title: Prevalence of K-Ras mutations in hepatocellular carcinoma: A Turkish Oncology Group pilot study.
abstract: Hepatocellular carcinoma (HCC) is the fifth most common male-predominant type of cancer worldwide. There is no effective treatment regimen available for advanced-stage disease and chemotherapy is generally ineffective in these patients. The number of studies on the prevalence of K-Ras mutations in HCC patients is currently limited. A total of 58 patients from 6 comprehensive cancer centers in 4 metropolitan cities of Turkey were enrolled in this study. Each center committed to enroll approximately 10 random patients whose formalin-fixed paraffin-embedded tumor tissues were available for K-Ras, exon 2 genotyping. Two methods were applied based on the availability of adequate amounts of tumor DNA. In the first method, the samples were processed using TheraScreen. The genomic DNA was further used to detect the 7 most frequent somatic mutations (35G>A; 35G>C; 35G>T; 34G>A; 34G>C; 34G>T and 38G>A) in codons 12 and 13 in exon 2 of the K-Ras oncogene by quantitative polymerase chain reaction (PCR). In the second method, the genomic DNA was amplified by PCR using primers specific for K-Ras exon 2 with the GML SeqFinder Sequencing System's KRAS kit. The identified DNA sequence alterations were confirmed by sequencing both DNA strands in two independent experiments with forward and reverse primers. A total of 40 samples had adequate tumor tissue for the mutation analysis. A total of 33 (82.5%) of the investigated samples harbored no mutations in exon 2. All the mutations were identified via a direct sequencing technique, whereas none were identified by TheraScreen. In conclusion, in our patients, HCC exhibited a remarkably low (<20%) K-Ras mutation rate. Patients harboring K-Ras wild-type tumors may be good candidates for treatment with epidermal growth factor inhibitors, such as cetuximab.
authors.affiliation: Department of Medical Oncology, Marmara University, Faculty of Medicine, 34722 Istanbul, Turkey.
authors.forename: Nazim Serdar
authors.initials: NS
authors.lastname: Turhal
authors.affiliation: Department of Pathology, Ankara University, Faculty of Medicine, 06100 Ankara, Turkey.
authors.forename: Berna
authors.initials: B
authors.lastname: Savaş
authors.affiliation: Department of Pathology, Ankara University, Faculty of Medicine, 06100 Ankara, Turkey.
authors.forename: Öznur
authors.initials: Ö
authors.lastname: Çoşkun
authors.affiliation: Department of Pathology, Marmara University, Faculty of Medicine, 34899 Istanbul, Turkey.
authors.forename: Emine
authors.initials: E
authors.lastname: Baş
authors.affiliation: Department of Medical Oncology, Ege University, Faculty of Medicine, 35100 Izmir, Turkey.
authors.forename: Bülent
authors.initials: B
authors.lastname: Karabulut
authors.affiliation: Department of Pathology, Ege University, Faculty of Medicine, 35100 Izmir, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Nart
authors.affiliation: Department of Medical Oncology, Acibadem University, Faculty of Medicine, Maslak Hospital, 34662 Istanbul, Turkey.
authors.forename: Taner
authors.initials: T
authors.lastname: Korkmaz
authors.affiliation: Department of Pathology, Kartal Training and Research Hospital, 34890 Istanbul, Turkey.
authors.forename: Dilek
authors.initials: D
authors.lastname: Yavuzer
authors.affiliation: Department of Medical Oncology, Bilim University, Faculty of Medicine, 34340 Istanbul, Turkey.
authors.forename: Gökhan
authors.initials: G
authors.lastname: Demir
authors.affiliation: Department of Pathology, Bilim University, Faculty of Medicine, 34340 Istanbul, Turkey.
authors.forename: Gülen
authors.initials: G
authors.lastname: Doğusoy
authors.affiliation: Department of Medical Oncology, Necmettin Erbakan University, Meram Faculty of Medicine, 42080 Konya, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Artaç
keywords: K-Ras expression; cetuximab; hepatocellular carcinoma; mutation analysis