Methods of predicting cancer risk using gene expression in premalignant tissue
View Patent ↗The present disclosure provides methods for assessing a patient's cancer risk and/or recurrence risk, which methods comprise assaying, in a biological sample obtained from the gastrointestinal (GI) tract of the patient, an expression level of a risk gene. The present disclosure also provides methods involving a cancer risk/recurrence risk sequence, i.e. the V600E mutation of the BRAF gene, which is useful for assessing cancer risk and/or recurrence risk in a patient.
1. A method for determining cancer risk for a human patient, comprising:
analyzing a sequence of BRAF in a tissue sample obtained from a premalignant lesion from the lower gastrointestinal (GI) tract of the patient to detect a V600E mutation;
measuring a level of an RNA transcript of DUSP6, or its expression product, in the tissue sample;
normalizing the level of the RNA transcript of DUSP6, or its expression product, against an expression level of at least one reference gene, to obtain a normalized expression level of DUSP6,
comparing the normalized expression level of DUSP6 from the patient to the normalized expression level of DUSP6 in a population with no cancer; and
determining that the patient has an increased cancer risk if the normalized expression level of DUSP6 from the patient is increased, or that the patient has a decreased cancer risk if the normalized expression level of DUSP6 from the patient is decreased.
2. The method of claim 1 , wherein the premalignant lesion comprises a colorectal polyp with low grade dysplasia.
3. The method of claim 2 , wherein said cancer risk is a synchronous risk.
4. The method of claim 2 , wherein said cancer risk is a progression risk.
5. The method of claim 1 , wherein said measuring step is conducted using quantitative polymerase chain reaction.
6. The method of claim 1 , wherein the measuring step quantifies an RNA transcript of DUSP6.
7. The method of claim 1 , wherein the measuring step quantifies a polypeptide level of DUSP6.
8. The method of claim 1 , further comprising using the normalized expression level of DUSP6 to generate a score indicative of the cancer risk for the patient.
9. The method of claim 8 , wherein the score provides information concerning a likelihood that the patient has a co-existent malignant lesion of the lower GI tract.
10. The method of claim 8 , wherein the score provides information concerning a likelihood that the patient will develop a malignant lesion in the lower GI tract.
11. The method of claim 1 , wherein the premalignant lesion comprises a colorectal polyp.
12. The method of claim 1 , wherein the tissue sample is obtained from a biopsy.
13. The method of claim 1 , wherein the cancer risk is colorectal cancer risk.
14. A method for determining cancer risk for a human patient, comprising:
extracting RNA from a tissue sample obtained from a premalignant lesion from the lower gastrointestinal (GI) tract of the patient;
analyzing a sequence of BRAF from the tissue sample to detect a V600E mutation;
reverse transcribing an RNA transcript of DUSP6 to produce a cDNA of DUSP6;
amplifying the cDNA of DUSP6;
producing an amplicon of the RNA transcript of DUSP6;
assaying a level of the amplicon of the RNA transcript of DUSP6;
normalizing the amplicon level of the RNA transcript of DUSP6 against an amplicon level of at least one reference RNA transcript in the tissue sample to provide a normalized amplicon level of DUSP6,
comparing the normalized amplicon level of DUSP6 from the patient to the normalized amplicon level of DUSP6 in a population with no cancer; and
determining that the patient has an increased cancer risk if the normalized amplicon level of DUSP6 from the patient is increased, or that the patient has a decreased cancer risk if the normalized amplicon level of DUSP6 from the patient is decreased.
15. The method of claim 14 , wherein the premalignant lesion comprises a colorectal polyp with low grade dysplasia.
16. The method of claim 14 , wherein the premalignant lesion comprises a colorectal polyp.
17. The method of claim 14 , wherein the amplifying step is performed by polymerase chain reaction.
18. The method of claim 14 , wherein the cancer risk is colorectal cancer risk.