[1677] RAS Mutational Analysis in 9334 Solid and Hematopoietic Malignancies.

Deqin Ma, Rajyalakshmi Luthra, Su S Chen, Cameron C Yin, Rachel L Sargent, Keyur P Patel, Jeffrey Medeiros, Zhuang Zuo. The U of Texas M. D. Anderson Cancer Center, Houston

Background: Transforming mutations of RAS oncogenes are present in 15% of human cancers and serve as predictors for therapeutic response and tumor progression. The distribution of RAS mutations varies in different malignancies, suggesting that the RAS oncogenes function differently in various tumors. To characterize the variable frequency and site distribution of RAS mutations, we identified and reviewed 9334 solid and hematopoietic malignancies tested for KRAS and NRAS mutations within our institution from 2000-2010.
Design: Genomic DNA was isolated from bone marrow, peripheral blood or micro-dissected formalin-fixed, paraffin-embedded tissue patient samples. Mutational analysis of codons 12, 13, and 61 of the KRAS and NRAS genes was carried out by PCR amplification followed by pyrosequencing using the PSQ96 HS system (Biotage AB, Uppsala, Sweden).
Results: 5200 hematopoietic malignancies and 4134 solid tumors analyzed for KRAS and NRAS mutations were identified. 1037 (25%) KRAS and 149 (4%) NRAS mutations were identified in solid tumors. Of all the RAS mutations identified in solid tumors, 820/1186 (70%) occurred in codon 12 of KRAS (K12). K12 and KRAS codon 61 (K61) mutations were found in 156 (13%) and 61 (5%) of patients, respectively. KRAS mutations most frequently occurred in colon cancer (39%), followed by lung cancer (19%) and melanoma (8%). In hematopoietic malignancies, 107 (2%) KRAS and 300 (6%) NRAS mutations were documented. NRAS codon 12 (N12) mutations were detected in 210 cases (52%). NRAS codon 13 (N13) and NRAS 61 (N61) mutations were found in 63 (15%) and 27 (7%) cases, respectively, with the highest mutation rate seen in chronic myelomonocytic leukemia (30%), followed by acute myeloid leukemia (8%).
Conclusions: Mutations in the RAS oncogene family constitute a common oncogenic mechanism in cancers across different organ systems. Our study shows that the mutation frequency and site differs greatly between and within various malignancies.
Category: Pathobiology

Wednesday, March 2, 2011 9:30 AM

Poster Session V # 230, Wednesday Morning

 

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