title: KRASmutational concordance between primary and metastatic colorectal adenocarcinoma.
abstract: KRASmutation analysis is commonly performed on tissue samples obtained from primary colorectal cancers (CRCs). The metastatic lesions of CRC are usually considered as qualitatively similar or even identical to the primary tumors. The aim of this study was to evaluate the spectrum and distribution ofKRASmutations in a large collection of CRCs, while also evaluating the concordance of primary and metastatic lesions among available paired specimens from the same patients. A total of 729 patients with histologically confirmed advanced CRC at the University Hospital and Local Health Unit (Sassari, Italy) were included. Clinical and pathological features were obtained from medical records and/or pathology reports. Formalin-fixed, paraffin-embedded tissue samples were used for mutation analysis. Genomic DNA was isolated using a standard protocol; the coding sequence and splice junctions of exons 2 and 3 in theKRASgene were screened by direct automated sequencing. Overall, 219 (30%)KRASmutations were found; 208 (30.1%) were identified in the 690 primary tumors and 11 (28.2%) in the 39 metastatic tissue samples. Among the 31 (4.3%) patients who had paired samples of primary CRC and synchronous or asynchronous metastases, 28 (90.3%) showed consistent mutation patterns between the primary tumors and metastatic lesions. In one case, an additive mutation (Q61L) was found in the metastatic tissue, while two other discrepant cases exhibited a different mutation distribution; Q61H in the primitive lesion and G13V in the metastatic lesion in one case, and a mutated primary tumor (Q61L) and wild-type metastasis in another case. The results of this study confirm that a high concordance exists between the results ofKRASmutation analysis performed in primitive and metastatic CRCs; independent subclones may be generated in a limited amount of patients.
authors.affiliation: Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Sassari I-07100, Italy.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Paliogiannis
authors.affiliation: Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Sassari I-07100, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.affiliation: Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Sassari I-07100, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Tanda
authors.affiliation: Institute of Biomolecular Chemistry, Cancer Genetics Unit, National Research Council, Sassari I-07040, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
authors.affiliation: Institute of Biomolecular Chemistry, Cancer Genetics Unit, National Research Council, Sassari I-07040, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Palomba
keywords: KRAS gene; colorectal cancer; mutation analysis