ADDENDUM (K-RAS MOLECULAR DIAGNOSTIC FINDINGS):
MOLECULAR DIAGNOSTIC FINDINGS:
THIS TEST WAS PERFORMED BY THE UNIVERSITY OF FLORIDA DIAGNOSTIC REFERENCE LABORATORIES.



ADENOCARCINOMA IDENTIFIED ON H&E SLIDE.

KRAS MUTATION ANALYSIS:


SUMMARY OF RESULTS:
GENE  VALUE          INTERPRETATION


INTERPRETATION:


TEST DESCRIPTION:
THE TEST DETECTS 7 KRAS GENE MUTATIONS AT CODON 12 AND 13, THE MUTATIONS AT THESE TWO CODONS ARE LINKED TO RESISTANCE TO CANCER THERAPIES THAT TARGET TO THE EGFR PATHWAY IN COLORECTAL AND OTHER CANCERS. TO DETECT THE GENE MUTATION, TISSUE CONTAINS HIGH PERCENTAGE OF TUMOR ARE MANUALLY DISSECTED FROM A FORMALIN-FIXED, PARAFFIN-EMBEDDED SPECIMEN. DNA IS ISOLATED FROM THE DISSECTED TISSUE, KRAS CODON 12 AND 13 REGION IS PCR AMPLIFIED, AND PYROSEQUENCE IS USED FOR THE MUTATION DETECTION.
MUTATIONS THAT CAN BE DETECTED IN THIS TEST: GLY12SER (C.34 G>A), GLY12CYS (C.34 G>T), GLY12ARG (C.34 G>C), GLY12ASP (C.35 G>A), GLY12VAL (C.35 G>T), GLY12ALA (C.35 G>C), GLY13ASP (C.38 G>A).

REFERENCES:
1. K-RAS MUTATION DETECTION IN COLORECTAL CANCER USING THE PYROSEQUENCING TECHNIQUE
PATHOLOGY – RESEARCH AND PRACTICE 203 (2007) 489–497ANGELA POEHLMANN, DOERTHE KUESTER, FRANK MEYER, HANS LIPPERT, ALBERT ROESSNER AND REGINE SCHNEIDER-STOCK

2. SENSITIVE SEQUENCING METHOD FOR KRAS MUTATION DETECTION BY PYROSEQUENCING JOURNAL OF MOLECULAR DIAGNOSTICS, VOL. 7, NO. 3, AUGUST 2005 SHUJI OGINO, TAKAKO KAWASAKI, MOHAN BRAHMANDAM, LIYING YAN, MAMI CANTOR, CHUNGDAK NAMGYAL, MARI MINO-KENUDSON, GREGORY Y. LAUWERS, MASSIMO LODA AND CHARLES S. FUCHS

3. KRAS MUTATION STATUS IS PREDICTIVE OF RESPONSE TO CETUXIMAB THERAPY IN COLORECTAL CANCER. CANCER RES. 2006;66(8):3992-3995. LIEVRE A, BACHET JB, LE CORRE D, ET AL.

4. EXPRESSION OF EPIREGULIN AND AMPHIREGULIN AND K-RAS MUTATION STATUS PREDICT DISEASE CONTROL IN METASTATIC COLORECTAL CANCER PATIENTS TREATED WITH CETUXIMAB. J CLIN ONCOL. 2007;25(22):3230-3237. KHAMBATA-FORD S, GARRETT CR, MEROPOL NJ, ET AL.

5. WILD-TYPE KRAS IS REQUIRED FOR PANITUMUMAB EFFICACY IN PATIENTS WITH METASTATIC COLORECTAL CANCER. J CLIN ONCOL. 2008;26(10):1626-1634. AMADO RG, WOLF M, PEETERS M, ET AL.

6. KRAS STATUS AND EFFICACY IN THE FIRST-LINE TREATMENT OF PATIENTS WITH METASTATIC COLORECTAL CANCER (MCRC) TREATED WITH FOLFIRI WITH OR WITHOUT CETUXIMAB: THE CRYSTAL EXPERIENCE. IN: PROGRAM AND ABSTRACTS OF THE 44RD AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING; MAY 30-JUNE 3, 2008; CHICAGO, IL. ABSTRACT 2. VAN CUTSEM E, LANG I, D’HAENS G, ET AL.

7. AN UPDATED ANALYSIS OF SAFETY AND EFFICACY OF OXALIPLATIN (OX)/BEVACIZUMAB (BEV) +/- PANITUMUMAB (PMAB) FOR FIRST-LINE TREATMENT (TX) OF METASTATIC COLORECTAL CANCER (MCRC) FROM A RANDOMIZED CONTROLLED TRIAL (PACCE). IN: PROGRAM AND ABSTRACTS OF THE 2008 GASTROINTESTINAL CANCERS SYMPOSIUM; JANUARY 25-27, 2008; ORLANDO, FL. ABSTRACT 273. HECHT JR, MITCHELL E, CHIDIAC T, ET AL.

8. AMERICAN SOCIETY OF CLINICAL ONCOLOGY PROVISIONAL CLINICAL OPINION: TESTING FOR KRAS GENE MUTATIONS IN PATIENTS WITH METASTATIC COLORECTAL CARCINOMA TO PREDICT RESPONSE TO ANTI-EPIDERMAL GROWTH FACTOR RECEPTOR MONOCLONAL ANTIBODY THERAPY. ALLEGRA CJ, JESSUP JM, SOMERFIELD MR, ET AL.

9. A GENETIC MODEL FOR COLORECTAL TUMORIGENESIS. CELL. 1990;61(5):759-767. FEARON ER, VOGELSTEIN B.

10. NOVEL BIOMARKERS FOR TUMOR DETECTION AND PROGRESSION. IN: PROGRAM AND ABSTRACTS OF THE 2008 AMERICAN ASSOCIATION FOR CANCER RESEARCH 2008 ANNUAL MEETING; APRIL 12-16, 2008; SAN DIEGO, CA. ABSTRACT 1181. JUAN T, SUGGS S, WOLF M, ET AL.

11. REF NM_033360.2 HOMO SAPIENS V-KI-RAS2 KIRSTEN RAT SARCOMA VIRAL ONCOGENE HOMOLOG (KRAS), TRANSCRIPT VARIANT A, MRNA.

THE PERFORMANCE CHARACTERISTICS OF THIS TEST WERE VALIDATED BY UNIVERSITY OF FLORIDA-DRL LABORATORIES. THE U.S. FOOD AND DRUG ADMINISTRATION (FDA) HAS NOT APPROVED OR CLEARED THIS TEST. HOWEVER, FDA APPROVAL OR CLEARANCE IS CURRENTLY NOT REQUIRED FOR CLINICAL USE OF THIS TEST. THE RESULTS ARE NOT INTENDED TO BE USED AS THE SOLE MEANS FOR CLINICAL DIAGNOSIS OR PATIENT MANAGEMENT DECISIONS. UF-DRL IS AUTHORIZED UNDER CLINICAL LABORATORY IMPROVEMENT AMENDMENTS (CLIA) AND BY ALL STATES TO PERFORM HIGH-COMPLEXITY TESTING.