KRAS Mutation in Lipomas, Atypical Lipomatous Tumors/Well-Differentiated Liposarcomas (ALT) and Dedifferentiated Liposarcomas (DDLS)
Chi Young Ok, Matthew Welch, Keith Tomaszewicz, Lloyd Hutchinson, Ediz F Cosar. University of Massachusetts Memorial Medical Center, Worcester, MA
Background: Mutations in members of the RAS family of oncogenes (KRAS, HRAS, and NRAS) occur in many cancers. HRAS mutations have been studied in well-differentiated liposarcoma and DDLS. However, KRAS mutation status is not well-studied in lipomatous tumor and reports are few, if any. Herein, we report KRAS mutation status in lipoma, ALT and DDLS cases diagnosed in our institution.
Design: We searched the pathology archives of our hospital during 2002 to 2011 and randomly selected 21 cases of lipoma, 9 cases of ALT and 6 cases of DDLS to examine KRAS mutation status. Areas of tumor were identified and microdissected from formalin-fixed, paraffin-embedded tissue in all cases. Two different areas, one with ALT-like and one with poorly differentiated sarcomatous features, were selected in one case of DDLS to compare mutational status. KRAS mutation on codons 12 & 13 was tested by peptide nucleic acid (PNA)-clamp quantitative PCR and reflexed to direct Sanger sequencing when PCR was positive.
Results: The median ages of patients are 49, 67 and 76.5 years old with lipoma, ALT and DDLS, respectively. There is no gender predilection in all groups. The location of lipoma and DDLS was diverse, but ALT shows predilection for thigh (66%, 6/9). Out of 21 cases of lipoma, one case (4.8%) showed Gly12Val (GGT>GTT) KRAS mutation. In ALT group, one case (11.1%) showed Gly12Cys (GGT>TGT) KRAS mutation. KRAS mutation was not found in DDLS.
Conclusions: Although the number of cases in this study is low, activating KRAS mutations involving codons 12 & 13 appear to be rare in lipomatous tumors. This result contrasts with a report of frequent (21%, 4/19) HRAS mutations in DDLS. A comprehensive analysis of lipomatous tumors including global genetics and/or epigenetic approaches targeting a variety of oncogenic pathways (e.g. RAS, JAK, PIK3CA, or WNT) is needed to reveal the primary oncogenic trigger.
Category: Bone & Soft Tissue
Monday, March 19, 2012 1:00 PM
Poster Session II # 8, Monday Afternoon