公开(公告)号：US11981959B2

公开(公告)日：2024-05-14

申请号：US17748522

申请日：2022-05-19

Applicant: MORGAN AND MENDEL GENOMICS, INC. ,  ALBERT EINSTEIN COLLEGE OF MEDICINE

Inventor： Harry Ostrer ,  Johnny C. Loke ,  Ishraq Alim

IPC: G01N31/00 ,  C12Q1/6804 ,  C12Q1/6827 ,  G01N15/14 ,  G01N33/50 ,  G01N33/53 ,  G01N33/574 ,  G01N15/10

CPC classification number: C12Q1/6827 ,  C12Q1/6804 ,  G01N15/14 ,  G01N33/5023 ,  G01N33/5035 ,  G01N33/5041 ,  G01N33/57419 ,  G01N33/57484 ,  G01N2015/1006

Abstract: Heritable pathogenic variants in the mismatch repair (MMR) pathway, also known as Lynch Syndrome (LS), can lead to the development of colon cancer and other cancers. Following mismatch, a complex of proteins consisting of MLH1, MSH2, MSH6 and PMS2 translocate into the nucleus to signal recruitment of repair mechanisms. Flow cytometry-based, functional variant assays (FVAs), were developed to determine whether variants in these MMR repair genes and/or other related genes would augment the nuclear translocation of MLH1 and MSH2 and downstream nuclear phosphorylation of ATM and ATR in response to DNA mismatches. Each assay distinguished pathogenic variants in MMR repair genes (MLH1, MSH2, PMS2 and MSH6) from benign controls. The combination of multiple assays provided robust separation between heterozygous pathogenic variant carriers and benign controls. The ability to produce distinct molecular phenotypes by these assays suggest FVA assays of MMR pathways could be used to identify LS and associated risk of colon and other cancers and could act as an adjunct to MMR gene sequencing panels in categorizing variants.

公开(公告)号：US20220260553A1

公开(公告)日：2022-08-18

申请号：US17674400

申请日：2022-02-17

Applicant: MORGAN AND MENDEL GENOMICS, INC. ,  ALBERT EINSTEIN COLLEGE OF MEDICINE

Inventor： Harry OSTRER ,  Johnny C. LOKE ,  Ishraq ALIM

IPC: G01N33/50 ,  G01N33/574 ,  G01N15/14

Abstract: Heritable pathogenic variants in the mismatch repair (MMR) pathway, also known as Lynch Syndrome (LS), can lead to the development of colon cancer and other cancers. Following mismatch, a complex of proteins consisting of MLH1, MSH2, MSH6 and PMS2 translocate into the nucleus to signal recruitment of repair mechanisms. Flow cytometry-based, functional variant assays (FVAs), were developed to determine whether variants in these MMR repair genes and/or other related genes would augment the nuclear translocation of MLH1 and MSH2 and downstream nuclear phosphorylation of ATM and ATR in response to DNA mismatches. Each assay distinguished pathogenic variants in MMR repair genes (MLH1, MSH2, PMS2 and MSH6) from benign controls. The combination of multiple assays provided robust separation between heterozygous pathogenic variant carriers and benign controls. The ability to produce distinct molecular phenotypes by these assays suggest FVA assays of MMR pathways could be used to identify LS and associated risk of colon and other cancers and could act as an adjunct to MMR gene sequencing panels in categorizing variants.

公开(公告)号：US20220341935A1

公开(公告)日：2022-10-27

申请号：US17748522

申请日：2022-05-19

Applicant: MORGAN AND MENDEL GENOMICS, INC. ,  ALBERT EINSTEIN COLLEGE OF MEDICINE

Inventor： Harry OSTRER ,  Johnny C. LOKE ,  Ishraq ALIM

IPC: G01N33/574 ,  C12Q1/6804

Abstract: Heritable pathogenic variants in the mismatch repair (MMR) pathway, also known as Lynch Syndrome (LS), can lead to the development of colon cancer and other cancers. Following mismatch, a complex of proteins consisting of MLH1, MSH2, MSH6 and PMS2 translocate into the nucleus to signal recruitment of repair mechanisms. Flow cytometry-based, functional variant assays (FVAs), were developed to determine whether variants in these MMR repair genes and/or other related genes would augment the nuclear translocation of MLH1 and MSH2 and downstream nuclear phosphorylation of ATM and ATR in response to DNA mismatches. Each assay distinguished pathogenic variants in MMR repair genes (MLH1, MSH2, PMS2 and MSH6) from benign controls. The combination of multiple assays provided robust separation between heterozygous pathogenic variant carriers and benign controls. The ability to produce distinct molecular phenotypes by these assays suggest FVA assays of MMR pathways could be used to identify LS and associated risk of colon and other cancers and could act as an adjunct to MMR gene sequencing panels in categorizing variants.