NRAS Mutational Analysis
Description
NRAS is a signaling intermediate in the growth receptor pathway. Certain NRAS mutations predict poor response to anti-EGFR therapy in patients with metastatic colorectal cancer.
KRAS (NAACCR Data Item # 3866) and NRAS are important signaling intermediates in the growth receptor pathway, which controls cell proliferation and survival. Both KRAS and NRAS may be constitutively activated through mutation during colorectal carcinogenesis so that they continuously stimulate cell proliferation and prevent cell death (reference AJCC 8, pg. 266). KRAS and NRAS mutations predict poor response to anti-EGFR therapy in patients with metastatic colon cancer. AJCC 8 estimates that KRAS may be activated in up to 40% and NRAS in about 7% of colorectal carcinomas.
Rationale
NRAS mutational analysis is recommended in clinical guidelines for patients with metastatic colon cancer who are being considered for anti-EGFR therapy. It is a new data item for cases diagnosed 1/1/2021+.
Additional Info
**Source documents:** pathology report, clinical laboratory report
For further information, refer to the **Colon and Rectum Biomarker** Reporting cancer protocol published by the College of American Pathologists for the AJCC Staging System *Colon and Rectum*
Notes
**Note 1:** **Effective years**
* This SSDI is effective for diagnosis years 2021+
* For cases diagnosed 2018-2020, this SSDI must be blank
**Note 2:** **Physician Statement**
* Physician statement of NRAS can be used to code this data item when no other information is available.
**Note 3:** **Applicable stages**
* NRAS may be recorded for all stages; however, it is primarily performed for patients with metastatic disease. If information is not available, code 9.
**Note 4:** **Results from nodal or metastatic tissue**
* Results from nodal or metastatic tissue may be used for NRAS.
**Note 5:** **Neoadjuvant Therapy**
* Record the assay from tumor specimens prior to neoadjuvant therapy.
* If neoadjuvant therapy is given and there are no NRAS results from pre-treatment specimens, report the findings from post-treatment specimens.
Coding Guidelines
There are 3 NRAS codons that are commonly mutated in colorectal cancers. This SSDI does not record the actual mutation, but instead records the codon or codon group that contains the mutation. If a specific NRAS mutation is reported, its codon may be identified from the following list of common NRAS mutations grouped by codon.
**1)** **Codon 12 (See code 1)**
+ **a.** Gly12Asp (GGT>GAT)
+ **b.** Gly12Val (GGT>GTT)
+ **d.** Gly12Cys (GGT>TGT)
+ **e.** Gly12Ser (GGT>AGT)
+ **f.** Gly12Ala (GGT>GCT)
+ **g.** Gly12Arg (GGT>CGT)
+ **h.** Codon 12 mutation, not otherwise specified
**2)** **Codon 13 (See code 1)**
+ **a.** Codon 13 mutation, not otherwise specified
**3)** **Codon 61 (See code 1)**
+ **a.** Gln61Lys (CAA>AAA)
+ **b.** Gln61Arg (CAA>CGA)
+ **c.** Codon 61 mutation, not otherwise specified
**4)** **Other specified codons (excluding 12, 13, 61) (See code 2)**
**5)** **Unknown codon (See code 4)**
* **a.** NRAS positive, specific codon not mentioned
**6)** **Code 9** when
* **a.** Insufficient amount of tissue available to perform test
* **b.** No microscopic confirmation of tumor
* **c.** Pathology report available and there is no mention of NRAS
* **d.** NRAS not ordered or not done, or unknown if ordered or done
Default
8
Metadata
SSDI 2021–
| Code |
Description |
| 0 |
Normal
NRAS negative; NRAS wild type
Negative for (somatic) mutations, no alterations, no (somatic) mutations identified, not present, not detected |
| 1 |
Abnormal (mutated)/detected in codon(s) 12, 13, and/or 61 |
| 2 |
Abnormal (mutated)/detected, codon(s) specified but not in codon(s) 12, 13, or 61 |
| 4 |
Abnormal (mutated), NOS, codon(s) not specified |
| 7 |
Test ordered, results not in chart |
| 8 |
Not applicable: Information not collected for this case
(If this information is required by your standard setter, use of code 8 may result in an edit error.) |
| 9 |
Not documented in medical record
NRAS not assessed or unknown if assessed |
| <BLANK> |
Must be blank if diagnosis year is before 2021 |
