Image acquisition methods for simultaneously detecting genetic rearrangement and nuclear morphology

Abstract

In general, the presently disclosed technology relates to identification of cancer subtypes. More specifically, the technology relates to methods for determining molecular drivers of cancer and/or progression using a multivariate image data and statistical analysis of in-situ molecular markers and morphological characteristics in the same cells of a biological sample suspected of b cancer. This analysis takes place after a single acquisition that obtains the molecular and anatomic morphology data in parallel. The analysis compares specific morphological and molecular markers to known samples exhibiting particular genetic drivers of the cancer. This method provides statistical information that allows for an increased confidence in the identification of specific molecular drivers of the cancer.

1 . A multivariate cancer diagnostic method wherein said method determines the presence of both molecular markers and phenotypic morphological markers at the cellular level in a single cell or single sample containing a population of cells from a tissue, said method comprising:
 a. obtaining molecular marker data from a single sample from a subject comprising a single cell or population of cells from a tissue;   b. obtaining quantitative cell morphology data from the same single cell or population of cells as used in step (a) and performing a multivariable analysis of said single sample to generate a multivariable data set comprising both quantitative cell morphology data from step (b) and molecular marker data from step (a);   c. comparing the multivariable analysis data set obtained in step (b) with a reference multivariable analysis data set created by obtaining both molecular marker data and quantitative cell morphology data from cancer and non-cancer cell samples taken from individuals with known clinical outcome; and   d. predicting a clinical outcome defined by specific combinations of cell morphologic markers and molecular markers statistically associated with cancer progression, occurrence, metastases or other determinant of clinical outcome seen in the reference multivariable analysis data set.