Molecular Characteristics of Matched Primary Non-Small-Cell Lung Carcinomas (NSCLC) and Metastases to the Brain
E Benedettini, AG Saad, M Loda, LR Chirieac. Brigham and Women's Hospital, Boston, MA; Dana Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA
Background: Despite recent advances, the molecular mechanisms of brain metastasis remains poorly understood. The design of new targeted, patient-specific therapies requires knowledge of the presence of the molecular abnormalities that are present in both the primary tumor and distant metastatic sites. To determine whether the genetic profiles are constant between the primary lung cancers and their paired metastases we examined pairs of human primary and metastatic lung carcinomas by high-throughput gene mutation profiling.
Design: We evaluated formalin-fixed paraffin-embedded specimens from 21 patients (11 women [52%] and 10 men [48%], median age 65 years) with NSCLC metastatic to the brain and the corresponding primary primary NSCLC and brain metastases using the Sequenom mass spectrometry-based system (iPLEX protocol - OncoMap analysis) for 252 genetic mutations in ABL1, BRAF, EGFR, FGFR3, HRAS, KIT, KRAS, MET, NRAS, PDGFRA, PI3K, and RET. Some of the lower confidence mutations identified by iPLEX protocol were validated by homogeneous mass-extend (hME) technology.
Results: The results of molecular markers expression in the primary NSCLC and in metastatic brain NSCLC are summarized in table 1. In nine patients (39.1%) mutations were identified only in the primary lung tumors, in five patients (21.7%) mutations were identified only in the brain metastases, and in three patients (13%) mutations were identified in both lung and brain metastases. Except KRAS G12C mutation that was identified in two patients, all mutations identified were present in only one patient.
Results of various molecular markers in the primary NSCLC, metastatic brain NSCLC, or both
|Gene||Primary NSCLC||Metastatic NSCLC to brain||Present in Both Primary and Brain NSCLC|
|BRAF||D594G||D594G||D594G (one case)|
|EGFR||Exon19 del, D770_N771>AGG|
|KRAS||G12C||G12S; G12D; G12C||G12C (two cases)|
Conclusions: Our results showed that tumors have a great variation in their molecular abnormalities. Understanding the effect of these molecular differences between primary non-small-cell lung carcinomas and metastases to the brain will allow us to clarify the mechanism of metastatic progression of NSCLC to brain and potentially identify novel targets of therapy.
Category: Special Category for 2009 - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 230, Tuesday Morning