Concordance of KRAS, NRAS, BRAF, PIK3CA mutation status between the primary tumor and metastases in patients with colorectal cancer

If KRAS mutation status of primary colorectal tumor is representative of corresponding colorectal liver metastases (CRLM) mutational pattern, is controversial. Several studies have reported different rates of KRAS discordance, ranging from 4 to 32%. Aim of this study is to assess the incidence of discordance and its impact on overall survival (OS) in a homogenous group of patients. KRAS mutation status was evaluated in 107 patients resected for both primary colorectal tumor and corresponding CRLM at the same institution, between 2007 and 2018. Discordance rate was 15.9%. Its incidence varied according to the time interval between the two mutation analyses (p = 0.025; Pearson correlation = 0.2) and it was significantly higher during the first 6 months from the time of primary tumor evaluation. On multivariable analysis, type of discordance (wild-type in primary tumor, mutation in CRLM) was the strongest predictor of poor OS (p < 0.001). At multivariable logistic regression analysis, the number of CRLM >3 was an independent risk factor for the risk of KRAS discordance associated with the worst prognosis (OR = 4.600; p = 0.047). Results of our study suggested that, in the era of precision medicine, possibility of KRAS discordance should be taken into account within multidisciplinary management of patients with metastatic colorectal cancer.

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Comparison of KRAS mutation status between primary tumor and metastasis in Chinese colorectal cancer patients

Medical Oncology ◽

10.1007/s12032-016-0787-z ◽

2016 ◽

Vol 33 (7) ◽

Cited By ~ 4

Author(s):

Zhe-Zhen Li ◽

Long Bai ◽

Feng Wang ◽

Zi-Chen Zhang ◽

Fang Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Primary Tumor ◽

Kras Mutation ◽

Mutation Status ◽

Colorectal Cancer Patients ◽

Kras Mutation Status

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PIK3CA mutation status associated with improved tumor response to yttrium-90 radioembolization (Y90) of chemorefractory liver-dominant colorectal cancer (CRC) metastases

Journal of Vascular and Interventional Radiology ◽

10.1016/j.jvir.2015.12.399 ◽

2016 ◽

Vol 27 (3) ◽

pp. S153-S154

Author(s):

M. Bergen ◽

J. Erinjeri ◽

H. Yarmohammadi ◽

F. Boas ◽

E. Petre ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Response ◽

Pik3ca Mutation ◽

Mutation Status ◽

Yttrium 90

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Relationship between oncogenic mutations (RAS, BRAF and PIK3CA) and tumor location and prognosis in colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15109 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15109-e15109

Author(s):

Daisuke Inagaki ◽

Manabu Shiozawa ◽

Tetta Satoyoshi ◽

Yosuke Atsumi ◽

Masaaki Murakawa ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Braf Mutation ◽

Cox Regression ◽

Pik3ca Mutation ◽

Tumor Location ◽

Kras Mutations ◽

Mutation Status ◽

Cox Regression Analysis ◽

Oncogenic Mutation

e15109 Background: Several studies have reported that right-sided colon cancers (RCC) and left-sided colorectal cancers (LCRC) differ in several factors including genetic features. We investigated the difference in clinicopathological characteristics and oncogenic mutation status between patients with RCC and LCRC in all stages and assessed outcome. Methods: This study was a prospective, observational study. Patients were recruited from November 2014 to February 2016. Formalin-fixed paraffin-embedded tissue blocks were collected and DNA wes extracted from tissue sections from 227 cases. There was no double cancer. Mutations in KRAS, NRAS, HRAS, BRAF and PIK3CA were detected by next-generation DNA sequencer. Tumors from cecum to transverse colon were defined as RCC, and tumors from descending colon to rectum were defined as LCRC. The median follow-up period was 521 days. Results: KRAS, NRAS, BRAF and PIK3CA mutations were present in 95 patient (41.9%), 7 patients (3.1%), 10 patients (4.4%) and 23 patients (10.1%) respectively, and there was no HRAS mutation in all patients. RCC was 68 patients and LCRC was 159 patients. Poorly differentiated adenocarcinoma and mutinous adenocarcinoma were significantly more frequent in RCC compared to LCRC (P = 0.031). KRAS mutations were detected in 37 patients with RCC (54.4%) and in 58 patients with LCRC (36.5%). BRAF mutations were detected in 7 patient with RCC (10.3%) and in 3 patients with LCRC (1.9%). KRAS and BRAF mutation in RCC were significantly more frequent than in LCRC (P = 0.012 and P = 0.005, respectively). The incidence of NRAS and PIK3CA mutation was no difference between two groups. In all patients, overall survival was evaluated. On univariate Cox regression analysis, BRAF mutation was associated with significantly poorer overall survival than BRAF wild type (HR = 4.831, P = 0.013). Other oncogenic mutation status and tumor location weren’t associated with overall survival. Conclusions: KRAS and BRAF mutation were more frequent in the patients with RCC compared to those with LCRC in all stages. This study suggested BRAF mutation correlated with poor outcomes in patients with colorectal cancer.

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Tumor mutational burden of microsatellite stable metastatic colorectal tumors by patient factors and KRAS, BRAF, and PIK3CA mutation status.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.627 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 627-627 ◽

Cited By ~ 1

Author(s):

Jun Gong ◽

Marvin Sy ◽

Marwan Fakih

Keyword(s):

Colorectal Cancer ◽

Primary Tumor ◽

Pik3ca Mutation ◽

Older Individuals ◽

Colorectal Tumors ◽

Patient Factors ◽

Pik3ca Mutations ◽

Mutational Burden ◽

Tumor Mutational Burden ◽

Colorectal Cancer Patients

627 Background: Microsatellite instability (MSI) can predict response to pembrolizumab in metastatic colorectal cancer (mCRC). Benefit to PD-1 blockade is limited in microsatellite stable (MSS) mCRC yet MSS tumors represent >95% of all mCRC cases. Evidence suggests that high mutational load remains an important predictor of benefit to checkpoint inhibition across several tumors. We aimed to explore associations between tumor mutational burden (TMB) and various patient factors and mutations of interest to identify features of patients (pts) with MSS mCRC of potential significance to prognosis and PD-1 targeting. Methods: We conducted a retrospective study based on next-generation sequencing (NGS) of MSS metastatic colorectal tumors at our single institution using FoundationOne. TMB was categorized as high ≥ 20 mutations/megabase (Mb), intermediate 6-19 mutations/Mb, and low ≤ 5 mutations/Mb. TMB frequencies were analyzed according to age (≤50, >50, >65, and >70 years old), gender, race, location of primary tumor, and KRAS, BRAF, and PIK3CA mutations. Results: Among 194 MSS tumors with available TMB data, frequencies of tumors with intermediate TMB were significantly different in pts ≤50 years (24.6%, n=69) than in pts >65 (48.9%, n=47, Fisher’s exact (two-tailed) p=0.0096) and >70 (53.1%, n=32, p=0.0067). Frequencies of tumors with low TMB were significantly different in pts ≤50 years (75.4%, n=69) than in pts >65 (46.8%, n=47, p=0.0029) and >70 (43.8%, n=32, p=0.0032). Frequencies of high TMB tumors by age were 0% (≤50 years), 1.6% (>50), 4.3% (>65), and 3.1% (>70) and did not reach significance. Frequencies of high, intermediate, or low TMB tumors were not significantly different based on gender, race, and location of primary tumor. Frequencies of KRAS, BRAF, and PIK3CA mutations were similar across all TMB categories (p=0.7995, 0.8774, and 0.053, respectively). Conclusions: Older individuals with mCRC are less likely to have a low mutation burden by FoundationOne assay. Further validation of these findings in larger cohorts may indicate a potential higher likelihood for elderly colorectal cancer patients to benefit from immune-based strategies.

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