Gene signatures for cancer prognosis

Inventors

Stone, Steven • Gutin, Alexander • Wagner, Susanne • Reid, Julia

Assignees

Myriad Genetics Inc

Abstract

Biomarkers and methods using the biomarkers for classifying cancer in a patient (e.g., predicting the risk of cancer-specific death or cancer recurrence) are provided.

Core Innovation

A method is provided for treating a prostate cancer patient having an increased likelihood of cancer recurrence or cancer-specific death by measuring mRNA expression levels of a panel of genes comprising at least 3 test genes selected from Panel F, where one of the test genes is MCM10. The test genes of Panel F are ASF1B, ASPM, BIRC5, BUB1B, C18orf24, CDC2, CDC20, CDCA3, CDCA8, CDKN3, CENPF, CENPM, CEP55, DLGAP5, DTL, FOXM1, KIAA0101, KIF11, KIF20A, MCM10, NUSAP1, ORC6L, PBK, PLK1, PRC1, PTTG1, RAD51, RAD54L, RRM2, TK1, and TOP2A. A test expression score is then obtained by determining expression of each gene in the panel and incorporating each gene’s expression into the test expression score.

A test prognostic score is provided by combining the test expression score with at least one test clinical score representing at least one clinical variable, where the test prognostic score is calculated according to a formula comprising (A×test expression score)+(B×clinical score). In the described formulas, A=0.58 and the clinical score is the CAPRA score, with B=0.41. The prostate cancer patient is prognosed based on whether the test prognostic score exceeds or does not exceed a reference prognostic score, relating the prognostic classification to increased or no increased likelihood of cancer recurrence or cancer-specific death.

Based on the prognosis, one or more treatments are administered. For patients prognosed as having an increased likelihood, one or more of hormonal therapy, chemotherapy, radiation therapy, or surgery are administered. For patients prognosed as having no increased likelihood, active surveillance is administered, and further administering one or more of hormonal therapy, chemotherapy, radiation therapy, or surgery is based on the presence of prostate cancer symptoms and/or signs of accelerated prostate cancer growth.

Claims Coverage

The document includes two independent methods that both use a Panel F gene set, including MCM10, to generate a test expression score from mRNA measurements, combine it with a CAPRA-based clinical score using the linear formula (A×test expression score)+(B×clinical score) with A=0.58 and B=0.41, and make a treatment decision based on comparison to a reference prognostic score. The independent claims differ in whether treatment is escalated for increased risk or active surveillance is used when risk is not increased, and the latter claim further conditions additional therapy on symptoms/signs of accelerated growth.

Across both independent claims, Panel F mRNA measurements generate a test expression score, which is combined with a CAPRA clinical score using the specified linear formula (0.58×test expression score + 0.41×clinical score) to produce a test prognostic score. The treatment decision is based on whether the test prognostic score exceeds or does not exceed a reference prognostic score, leading either to administration of one or more therapies for increased risk or to active surveillance with further therapy conditioned on symptoms/signs of accelerated growth when risk is not increased.

Stated Advantages

Documented Applications