Mutational analysis and clinical correlation of metastatic colorectal cancer

Abstract

BACKGROUND Early identification of mutations may guide patients with metastatic colorectal cancer toward targeted therapies that may be life prolonging. The authors assessed tumor genotype correlations with clinical characteristics to determine whether mutational profiling can account for clinical similarities, differences, and outcomes. METHODS Under Institutional Review Board approval, 222 patients with metastatic colon adenocarcinoma (n = 158) and rectal adenocarcinoma (n = 64) who underwent clinical tumor genotyping were reviewed. Multiplexed tumor genotyping screened for >150 mutations across 15 commonly mutated cancer genes. The chi-square test was used to assess genotype frequency by tumor site and additional clinical characteristics. Cox multivariate analysis was used to assess the impact of genotype on overall survival. RESULTS Broad-based tumor genotyping revealed clinical and anatomic differences that could be linked to gene mutations. NRAS mutations were associated with rectal cancer versus colon cancer (12.5% vs 0.6%; P < .001) and with age ≥56 years (7% vs 0.9%; P = .02). Conversely, v-raf murine sarcoma viral oncogene homolog B (BRAF) mutations were associated with colon cancer (13% vs 3%; P = .024) and older age (15.8% vs 4.6%; P = .006). TP53 mutations were associated with rectal cancer (30% vs 18%; P = .048), younger age (14% vs 28.7%; P = .007), and men (26.4% vs 14%; P = .03). Lung metastases were associated with PIK3CA mutations (23% vs 8.7%; P = .004). Only mutations in BRAF were independently associated with decreased overall survival (hazard ratio, 2.4; 95% confidence interval, 1.09–5.27; P = .029). CONCLUSIONS The current study suggests that underlying molecular profiles can differ between colon and rectal cancers. Further investigation is warranted to assess whether the differences identified are important in determining the optimal treatment course for these patients.

Pattern and Dynamics of Distant Metastases in Metastatic Colorectal Cancer

“…To a certain extent, this observation may be driven by anatomy as the majority of colorectal cancers drain to the portal vein, thus promoting hematogenous spread to the liver [13]. Supporting this concept, the frequency of pulmonary metastases was increased in patients of our cohort with rectal cancer.…”

“…Further factors are likely to contribute to the site-specific appearance of metastases [13]. For example, certain alterations of the tumor cells appear to be associated with metastases to the lungs and lymph nodes [15,16].…”

Impact ofRASandBRAFmutations on carcinoembryonic antigen production and pattern of colorectal metastases

“…Tran et al [8] reported a higher rate of peritoneal and distant lymph node metastases and a lower rate of lung metastases in BRAF mutated tumors. Similarly, Russo et al [19] reported a higher likelihood of BRAF mutations in patients with distant lymph node metastases at the site of first recurrence. Finally, Kawazoe et al [12] retrospectively studied the clinical-pathological features of BRAF mutations in Japanese patients with metastatic CRC and found that peritoneal metastases are more frequently observed in BRAF mutated patients.…”

“…Several studies have reported an increased likelihood of peritoneal dissemination in BRAF mutant mCRC patients [8,9,19] . Yaeger et al [9] reported that patients with BRAF mutations were more likely to present with peritoneal metastases at initial diagnosis and less likely to have liver-limited metastases.…”

Częstość występowania mutacji somatycznych RAS w raku rdzeniastym tarczycy — analiza populacji polskiej

“…From the clinical point of view, screening for RAS mutations is important in patients with colorectal carcinoma where the presence of K-RAS mutation is associated with poor response to anti-EGFR therapies [26][27][28]. However, in differentiated thyroid cancer, the detection of RAS mutation has not thus far determined any treatment decision.…”