Compositions and methods for treating and diagnosing cancer

Abstract

The present invention relates to compositions and methods for treating, characterizing, and diagnosing cancer. In particular, the present invention provides gene expression profiles and signatures associated with solid tumor stem cells, as well as novel stem cell cancer markers useful for the diagnosis, characterization, prognosis and treatment of solid tumor stem cells. More particularly, the present invention identifies two profiles of cancer stem cells useful for the diagnosis, characterization, and treatment of cancer and cancer metastases. The invention also provides a variety of reagents such as stem cell gene signatures for use in the diagnosis and management of cancer.

1 . A method of classifying a solid tumor breast cancer comprising:
 (a) determining mRNA expression levels for genes: CDH1, MMP7, NOV, FOSL1, IL1R2, and FLJ20152 from a solid tumor breast cancer sample;   (b) comparing the determined mRNA expression levels of the genes in (a) to a pre-determined high risk expression profile, wherein the expression levels of CDH1, MMP7, NOV, FOSL1, and IL1R2 are low or undetectable in the pre-determined high risk expression profile compared to expression in normal breast tissue and the expression level of FLJ20152 is elevated in the pre-determined high risk expression profile compared to expression in normal breast tissue; and,   (c) classifying the cancer sample as high risk for a poor prognosis if the comparison in (b) is positively correlated or low risk for a poor prognosis if the comparison in (b) is negatively correlated.   
     
     
         2 . The method of  claim 1 , wherein the mRNA is detected using a DNA array comprising a polynucleotide that hybridizes to the mRNA. 
     
     
         3 . The method of  claim 1 , wherein the mRNA is detected using polymerase chain reaction comprising polynucleotide primers that specifically amplify the mRNA. 
     
     
         4 . The method of  claim 1 , wherein said determining further comprises determining the mRNA expression levels for one or more of SFRP1, KRT6B, G0S2, IL8, B3GNT5, FGFBP1, SHC1, ARNT, CYFIP2, C17orf27, TAP1, RNASEL, and LOC57168. 
     
     
         5 . The method of  claim 1 , wherein said determining further comprises determining the mRNA expression level for SHC1. 
     
     
         6 . The method of  claim 1 , wherein said determining further comprises determining the mRNA expression levels for: SFRP1, KRT6B, G0S2, IL8, B3GNT5, FGFBP1, SHC1, ARNT, CYFIP2, C17orf27, TAP1, RNASEL, and LOC57168. 
     
     
         7 . The method of  claim 1 , wherein said determining further comprises determining the mRNA expression levels for: SFRP1, KRT6B, G0S2, IL8, B3GNT5, FGFBP1, ARNT, CYFIP2, C17orf27, TAP1, RNASEL, and LOC57168. 
     
     
         8 . The method of  claim 1 , wherein said determining further comprises determining the mRNA expression levels for: SFRP1, KRT6B, IL8, B3GNT5, FGFBP1, SHCl, ARNT, CYFIP2, C17orf27, TAP1, RNASEL, and L0057168. 
     
     
         9 . The method of  claim 1 , wherein said determining further comprises determining the mRNA expression levels for: SFRP1, KRT6B, G0S2, IL8, FGFBP1, SHC1, CYFIP2, and TAP1. 
     
     
         10 . A method of classifying a solid tumor breast cancer comprising:
 (a) determining mRNA expression levels for genes: CDH1, MMP7, NOV, FOSL1, IL1R2, SFRP1, KRT6B, G0S2, IL8, B3GNT5, FGFBP1, SHC1, FLJ20152, ARNT, CYFIP2, C17orf27, TAP1, RNASEL, and LOC57168 from a solid tumor breast cancer sample;   (b) comparing the determined mRNA expression levels of the genes in (a) to a pre-determined high risk expression profile, wherein the expression levels of CDH1, MMP7, NOV, FOSL1, IL1R2, SFRP1, KRT6B, G0S2, IL8, B3GNT5 and FGFBP1 are low or undetectable in the pre-determined high risk expression profile compared to expression in normal breast tissue and the expression levels of SHC1, FLJ20152, ARNT, CYFIP2, C17orf27, TAP1, RNASEL and LOC57168 are elevated in the pre-determined high risk expression profile compared to expression in normal breast tissue; and,   (c) classifying the cancer sample as high risk for a poor prognosis if the comparison in (b) is positively correlated or low risk for a poor prognosis if the comparison in (b) is negatively correlated.   
     
     
         11 . A method of classifying a solid tumor breast cancer comprising:
 (a) determining mRNA expression levels for genes: CDH1, MMP7, NOV, FOSL1, IL1R2, SFRP1, KRT6B, IL8, FGFBP1, SHC1, FLJ20152, CYFIP2, and TAP1 from a solid tumor breast cancer sample;   (b) comparing the determined mRNA expression levels of the genes in (a) to a pre-determined high risk expression profile, wherein the expression levels of CDH1, MMP7, NOV, FOSL1, IL1R2, SFRP1, KRT6B, IL8, and FGFBP1 are low or undetectable in the pre-determined high risk expression profile compared to expression in normal breast tissue and the expression levels of SHC1, FLJ20152, CYFIP2, and TAP1 are elevated in the pre-determined high risk expression profile compared to expression in normal breast tissue; and,   (c) classifying the cancer sample as high risk for a poor prognosis if the comparison in (b) is positively correlated or low risk for a poor prognosis if the comparison in (b) is negatively correlated.   
     
     
         12 . The method of  claim 11 , further comprising:
 (d) determining the mRNA expression levels for B3GNT5, ARNT, C17orf27, RNASEL, and LOC57168;   (e) comparing the determined mRNA expression levels of the genes in (a) and (d) to a pre-determined high risk expression profile, wherein the expression levels of CDH1, MMP7, NOV, FOSL1, IL1R2, SFRP1, KRT6B, IL8, B3GNT5, and FGFBP1 are low or undetectable in the pre-determined high risk expression profile compared to expression in normal breast tissue and the expression levels of SHC1, FLJ20152, ARNT, CYFIP2, C17orf27, TAP1, RNASEL, and LOC57168 are elevated in the pre-determined high risk expression profile compared to expression in normal breast tissue; and   (f) classifying the cancer sample as high risk for a poor prognosis if the comparison in (e) is positively correlated or low risk for a poor prognosis if the comparison in (e) is negatively correlated.   
     
     
         13 . The method of  claim 11 , further comprising:
 (d) determining the mRNA expression level for G0S2;   (e) comparing the determined mRNA expression levels of the gene in (a) and (d) to a pre-determined high risk expression profile, wherein the expression levels of CDH1, MMP7, NOV, FOSL1, IL1R2, SFRP1, KRT6B, G0S2, IL8, and FGFBP1 are low or undetectable in the pre-determined high risk expression profile compared to expression in normal breast tissue and the expression levels of SHC1, FLJ20152, CYFIP2, and TAP1 are elevated in the pre-determined high risk expression profile compared to expression in normal breast tissue; and   (f) classifying the cancer sample as high risk for a poor prognosis if the comparison in (e) is positively correlated or low risk for a poor prognosis if the comparison in (e) is negatively correlated.