Method for detecting the presence of a gynaecological growth

Abstract

The invention relates to a method for detecting the presence of a gynaecological growth, in particular for the diagnosis of endometriosis. The invention also relates to a method of identifying a biomarker for detecting the presence of a gynaecological growth and to biomarkers identified by said method.

1 . A method for detecting the presence of a gynaecological growth which comprises the steps of:
 (i) determining the day or phase of the menstrual cycle;   (ii) taking body fluid samples at two or more different times during the menstrual cycle, characterised in that a first sample is taken during the menses phase of the menstrual cycle and a second sample is taken during the luteal phase of the menstrual cycle;   (iii) measuring nucleosomes or a component part thereof in the body fluid samples; and   (iv) using the levels of nucleosome or a component part thereof in, and the difference in biomarker levels between, the two samples as an indicator of the presence of a gynaecological growth.   
     
     
         2 . A method as defined in  claim 1 , wherein said first sample is taken during Days 1-5 of the menstrual cycle and said second sample is taken during the period commencing Day 18 of the menstrual cycle and ending with the onset of menses in the subsequent menstrual cycle. 
     
     
         3 . A method as defined in  claim 1 , wherein said first sample is taken during the time the subject is bleeding due to menstruation and said second sample is taken when the patient is not bleeding due to menstruation. 
     
     
         4 . A method as defined in any of  claims 1  to  3 , wherein said nucleosome or component part thereof comprises an intact nucleosome, a histone including a post-translationally modified histone, a histone variant or a nucleic acid including DNA or methylated DNA. 
     
     
         5 . A method as defined in any of  claims 1  to  4 , wherein said biomarker is released from the cells of a gynaecological growth. 
     
     
         6 . A method as defined in any of  claims 1  to  5 , wherein the step of determining the day or phase of the menstrual cycle is determined by reference to patient symptoms related to the menstrual cycle, such as temperature, pain and the onset or end of menstrual bleeding. 
     
     
         7 . A method as defined in any of  claims 1  to  5 , wherein the step of determining the day or phase of the menstrual cycle is determined by measurement of menstrual hormones or metabolites. 
     
     
         8 . A method for detecting the presence of a gynaecological growth which comprises the steps of:
 (i) administering to a subject an exogenous hormone, or hormone analogue, or hormone agonist, or hormone antagonist or a drug or contraceptive steroid or other substance intended to induce a gynaecological response in a stimulation or repression test; and   (ii) measuring nucleosomes or a component part thereof in a body fluid; and   (iii) determining whether the amount or nature of the nucleosomes or component part thereof present in the body fluid of the subject is altered by the administration of the said exogenous substance such that any cell death as detected by the release of nucleosomes or component part thereof, is associated with a gynaecological growth.   
     
     
         9 . A method as defined in  claim 8 , wherein said exogenous hormone comprises a contraceptive or other steroid. 
     
     
         10 . A method as defined in  claim 8  or  claim 9 , wherein said measurement comprises measurements before, at or near the time of administration. 
     
     
         11 . A method as defined in any of  claims 1  to  10 , wherein said body fluid is blood, menstrual blood or a derivative of blood including serum and plasma or urine. 
     
     
         12 . A method as defined in any of  claims 1  to  10 , wherein said body fluid is endometrial fluid. 
     
     
         13 . A method as defined in any of  claims 1  to  12 , wherein said gynaecological growth comprises endometriosis in a human or animal subject. 
     
     
         14 . A method as defined in any of  claims 1  to  13 , which is repeated on multiple menstrual cycles. 
     
     
         15 . A kit for diagnosing or monitoring endometriosis which comprises a ligand or binder specific for the nucleosome or component part thereof, or a structural/shape mimic of the nucleosome or component part thereof, together with instructions for use of the kit in accordance with any of the methods defined in  claims 1  to  14 . 
     
     
         16 . A kit as defined in  claim 15 , wherein said ligand or binder is specific for an intact nucleosome, a histone including a post-translationally modified histone, a histone variant or a nucleic acid including DNA or methylated DNA. 
     
     
         17 . A method for identifying a nucleosome component biomarker for detecting the presence of a gynaecological growth which comprises the steps of:
 (i) determining the day or phase of the menstrual cycle;   (ii) taking body fluid samples at two or more different times during the menstrual cycle, characterised in that a first sample is taken during the menses phase of the menstrual cycle and a second sample is taken during either the follicular or luteal phase of the menstrual cycle;   (iii) measuring nucleosomes or a component part thereof in said first and second samples; and   (iv) determining whether the amount or nature of nucleosomes or component part thereof is controlled or influenced by the menstrual cycle, such that control or influence indicates the identity of a biomarker.   
     
     
         18 . A biomarker identified by the method as defined in  claim 17 .