Molecular Testing Lends Knowledge to Mutation Profile in Patients with Colorectal Cancer

Molecular testing provided the clinical data and mutation profile of Chinese patients with colorectal cancer in this retrospective study.

A Chinese study published in Cancer Medicine indicated that molecular testing offered the clinical data and mutation profile of Chinese patients with colorectal cancer (CRC), lending knowledge to gene mutation patterns and the role they may play in the disease.

The information from these mutated genes may also aid in the research and development of new drugs for CRC.

“As a pathologically and clinically heterogeneous disease, CRC presents different clinical features, treatment response, and prognosis. Hence, it is necessary to find out clinical or molecular markers which may have prognostic or predictive value,” the researchers wrote.

In this retrospective study of 1190 Chinese patients with CRC, 582 (48.9%) cases were detected with gene mutations. Of those cases, there were 111 (19.7%) cases with 2 concurrent mutations and 6 (1%) cases with 3 concurrent mutations.

KRAS was the most common gene mutation that occurred in all cases (36.1%), followed by PIK3CA (10.2%), NRAS (3.9%), BRAF (2.9%), HRAS (0.9%), and EGFR (0.9%). AKT1, KIT, FGFR1, FGFR3, FLT3, CDK, ERBB2, ABL1, MET, RET, and PDGFRA mutations were extremely rare in CRC. KRAS, NRAS, PIK3CA, and BRAF mutations were not associated with prognosis; however, the BRAF mutation was associated with poor prognosis in patients who accepted anti-EGFR therapy.

“Though CRC is considered a sporadic disease, it has been proved to be associated with genetic variants, including microsatellite instability (MSI), chromosomal instability, and RAS-RAF-MAPK mutation. It has been suggested that molecular biomarkers, such as KRAS, BRAF, PIK3CA, may have prognostic value in CRC,” the researchers wrote.

The primary tumor site was defined by 2 categories: right-sided (from cecum to transverse colon) and left-sided (from spleen flexure to rectum). There were 283 right-sided and 901 left-sided cases; the other 6 patients had more than 1 primary tumor site and could not be classified to either right- or left-sided.

The majority of patients were diagnosed at a later stage (23.7% at stage III and 60.5% at stage IV). The most common metastatic tumor site was the liver (53.6%), followed by the lung (34.8%), peritoneum (26.6%), distant lymph nodes (22.2%), and bones (8.2%). Other metastatic tumor sites included were the ovaries, spleen, adrenal glands, skeletal muscles, etc.

Patients with the KRAS mutation were more likely to be female, with right-sided primary tumor location, well to moderate differentiation, and lung metastasis. However, these features were not associated with NRAS mutations. BRAF mutation was found in patients with poor differentiation. BRAFv600E mutation was associated with right-sided location. Neither KRAS, NRAS, BRAF, or PIK3CA were associated with tumor node metastasis (TNM) stage or MSI status.

Currently TNM is the most important prognostic factor in Chinese patients with CRC. However, even patients diagnosed with the same stage may have a different prognosis.

About 274,000 new CRC and 132,000 CRC-related deaths occurred in China in 2010, and those numbers are expected to almost double by 2025.


Ye Z-L, Qiu M-Z, Tang T, et al. Gene mutation profiling in Chinese colorectal cancer patients and its association with clinicopathological characteristics and prognosis. Cancer Med. doi:10.1002/cam4.2727.