Abstract: A method of diagnosing an MSI cancer in a patient including extracting and sequencing DNA from a tumoral sample and if available from a normal sample and operate an analyse of MNRs. The method is based on the demonstration that the FDA-approved NGS-based diagnostic test for identifying MSI in mCRC and nmCRC gave inaccurate results when compared with the gold standard reference methods. Consequently, whole exome sequencing (WES) data from all samples was further analyzed to improve detection of the MSI genomic signal in CRC and other primary tumor types. This allowed identification of weaknesses and limits of MSISensor and the design and validation of a newly optimized algorithm, namely MSICare. The high accuracy of MSICare for the detection of MSI in CRC and non-CRC tumors should allow it to become a future reference test for assessing MSI in pan-cancer.

Abstract: The present invention relates to the diagnostic of CMMRD. In the present work, the inventors aimed to develop a test that could drastically simplify and improve the diagnosis of CMMRD based on DNA sequence analysis of primary blood cells (PBCs) from patients. Using massive parallel sequencing, they explored the possibility that MSI, the main genomic and functional consequence of constitutive MMR-deficiency, was likely to occur in CMMRD PBCs well before any transformation. Thus the present invention relates to a method of diagnosing a CMMRD cancer or a MSI leukemia/lymphoma in a patient in need thereof.

Abstract: The present invention relates to methods for predicting the survival time of patients suffering from a micro satellite unstable cancer. In particular, the present invention relates to a method for predicting the survival time of a patient suffering from a micro satellite unstable cancer comprising i) determining the expression level of at least one gene encoding for an immune checkpoint protein in a tumor tissue sample obtained from the patient, ii) comparing the expression level determined at step i) with a predetermined reference value and iii) concluding that the patient will have a long survival time when the level determined at step i) is lower than the predetermined reference value or concluding that the patient will have a short survival time when the level determined at step i) is higher than the predetermined reference value.

Abstract: The invention relates to method for treating cancer. Through whole exome sequencing, the inventors analyzed 47 MSI CRC and results were confirmed in a series of 53 MSI CRC. Negatively selected coding alterations in MSI CRC were further investigated for their functional role in CRC cell lines and survival impact in a cohort of 164 MSI CRC patients. Five coding negatively selected, MSI-related mutational events were demonstrated to have deleterious effects on tumor expansion, while they were associated with worse prognosis inpatients. The inventors investigated the functional consequences of the silencing of WNK1, HMGXB4, GART, and/or PRRC2C using siRNA and/or shRNA in CRC cell lines in vitro and in vivo using xenograft models. Their inactivation in CRC cells led to deleterious effects on apoptosis, proliferation and/or cell migration. The deleterious effects were greatly enhanced when several of the targets were concomitantly silenced.

Abstract: The present invention relates to methods for predicting the survival time of patients suffering from a micro satellite unstable cancer. In particular, the present invention relates to a method for predicting the survival time of a patient suffering from a micro satellite unstable cancer comprising i) determining the expression level of at least one gene encoding for an immune checkpoint protein in a tumor tissue sample obtained from the patient, ii) comparing the expression level determined at step i) with a predetermined reference value and iii) concluding that the patient will have a long survival time when the level determined at step i) is lower than the predetermined reference value or concluding that the patient will have a short survival time when the level determined at step i) is higher than the predetermined reference value.

Abstract: The present invention relates to a mutated heat-shock protein 110 (HSP110) lacking its substrate binding domain, which does not exhibit its chaperon activity and/or is not capable of binding to best-shock protein 70 (HSP70) and/or to beat-shock protein 27 (HSP27), but which is capable of binding to a wild-type HSP110. Such a mutated heat-shock protein 110 can be used (i) in methods for proposing survival and/or the response to a treatment of a patient suffering from a cancer, more particularly from a cancer liable to have a microsatellite instability (MSI) phenotype, such as colorectal cancer (CRC), and (ii) for treating cancers.

Abstract: The present invention relates to a mutated heat-shock protein 110 (HSP110) lacking its substrate binding domain, which does not exhibit its chaperon activity and/or is not capable of binding to best-shock protein 70 (HSP70) and/or to beat-shock protein 27 (HSP27), but which is capable of binding to a wild-type HSP110. Such a mutated heat-shock protein 110 can be used (i) in methods for proposing survival and/or the response to a treatment of a patient suffering from a cancer, more particularly from a cancer liable to have a microsatellite instability (MSI) phenotype, such as colorectal cancer (CRC), and (ii) for treating cancers.

Abstract: The present invention relates to a mutated heat-shock protein 110 (HSP110) lacking its substrate binding domain, which does not exhibit its chaperone activity and/or is not capable of binding to heat-shock protein 70 (HSP70) and/or to heat-shock protein 27 (HSP27), but which is capable of binding to a wild-type HSP 110. Such a mutated heat-shock protein 110 can be used (i) in methods for prognosing survival and/or the response to a treatment of a patient suffering from a cancer, more particularly from a cancer liable to have a microsatellite instability (MSI) phenotype, such as colorectal cancer (CRC), and (ii) for treating cancers.