SNPMiner Trials by Shray Alag

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V1180L (1) V774A (1) T377M (1) V689M (1) V774M (1) D164V (1) L387M (1) R199W (1) N86S (1) M694V (1) N86Y (1) G11053T (1) R175H (1) T17M (1) Y86N (1) A2144G (1) A2059G (1) N345K (1) D50W (1) I180V (1) A864V (1) L24E (1) V118I (1) G212S (1) I843S (1) N1303K (1) R1623Q (1) A1033V (1) L1198F (1) N1325S (1) Q812R (1) V773M (1) G212A (1) A997T (1) S241T (1) E167K (1) G1764A (1) G80A (1) E62D (1) E274Q (1) M34T (1) G401S (1) A2142C (1) G1631D (1) G211A (1) D76Y (1) D76N (1) E384G (1) V249I (1) M1106C (1) L234I (1) L101I (1) A2143C (1) K806E (1) A687V (1) A119S (1) P1028S (1) A313G (1) D824V (1) S9C (1) C182A (1) S9G (1) S153F (1) S1900E (1) S1900D (1) S1900C (1) R1644H (1) S1900A (1) R702W (1) T1456G (1) T1565C (1) E1021K (1) K15210D (1) G779C (1) G82S (1) G779F (1) G840A (1) V18M (1) A27L (1) L28M (1) T351I (1) K121Q (1) L28P (1) H180Q (1) G779S (1) M11T (1) M11Q (1) P549S (1) N215S (1) G60D (1) R352W (1) G623R (1) G84E (1) E161K (1) G951A (1) C23S (1) E184K (1) V1206L (1) Y842C (1) V736A (1) L432V (1) E89Q (1) R135W (1) Y253F (1) G843D (1) D820Y (1) F77L (1) S311C (1) D10W (1) Y143H (1) G86R (1) Y143C (1) R112H (1) Y143A (1) A227G (1) K101Q (1) R463C (1) G85E (1) L236P (1) A310V (1) T798M (1) S310Y (1) R222C (1) A4917G (1) T798I (1) E44D (1) L302P (1) Q30R (1) L786V (1) R287Q (1) P286R (1) D36Y (1) R263Q (1) T599I (1) K103M (1) S680N (1) K1270A (1) R88Q (1) T224M (1) P46L (1) N700D (1) A5147S (1) E21G (1) Y822D (1) Q260A (1) Y188H (1) R131H (1) R1070Q (1) C316N (1) T81C (1) T1304M (1) I167V (1) I82A (1) D13H (1) Q54H (1) Q30H (1) L239R (1) Y823D (1) T117S (1) I84T (1) A222V (1) L106V (1) K432Q (1) G163S (1) I1370K (1) G163E (1) K650E (1) E757A (1) R399Q (1) G41S (1) C1895T (1) P392L (1) T334G (1) H274Y (1) R399G (1)

SNPMiner SNPMiner Trials (Home Page)


Report for Mutation N375S

Developed by Shray Alag, 2020-2021.
SNP Clinical Trial Gene

There are 2 clinical trials

Clinical Trials


1 A Biomarker-implemented Clinical Study Evaluating Mutations in MET and TP53 in a Population of Treatment-refractory Squamous Cell Carcinoma

Afatinib is approved therapy for SCC of the lung after progression with standard of care chemotherapy. There is also evidence of improvement of progression free survival of patients with metastatic/recurrent SCC of the head and neck after failure of chemotherapy in patients treated with afatinib. Therefore, treatment of patients with these 2 conditions with afatinib is not experimental, and will follow conventional clinical management.

NCT04533321
Conditions
  1. Squamous Cell Carcinoma
Interventions
  1. Drug: Afatinib
MeSH:Carcinoma Carcinoma, Squamous Cell
HPO:Carcinoma Squamous cell carcinoma

using immunohistochemistry.. MET-N375S mRNA copy number. --- N375S ---

Customised probes detecting wildtype MET allele or MET-N375S allele are designed to for genotyping (homozygous/heterozygous).. Presence of MET and HER2 amplification using fluorescence in situ hybridization (FISH). --- N375S ---

FFPE samples retrieved from patients genotyped with MET-N375S polymorphism will be subjected to MET and HER2 testing Abbott PathVysion DNA test kits. --- N375S ---

5. Clinical study will enroll patients genotyped positive for MET-N375S polymorphism. --- N375S ---

To determine the efficacy of afatinib in patients with germline MET-N375S polymorphism. --- N375S ---

2. To determine the tolerability of afatinib in chemo-relapsed patients with germline MET-N375S polymorphism. --- N375S ---

To determine the response rate of SCC HN/lung with Met-N375S to afatinib. --- N375S ---

Primary Outcomes

Description: using immunohistochemistry.

Measure: p-HER2 and p-MET status

Time: 3 years

Description: using RNAscope staining.

Measure: MET-N375S mRNA copy number

Time: 3 years

Description: DNA from the tumour specimens will be harvested for sequencing to identify cases with somatic mutations of TP53 gene. Changes in codon sequences will be reported. Germline DNA from the patients will be harvested from whole blood, and the polymorphic MET variant will be determined using ddPCR. Customised probes detecting wildtype MET allele or MET-N375S allele are designed to for genotyping (homozygous/heterozygous).

Measure: Identification of MET and TP53 mutations using droplet digital PCR (ddPCR) and Sanger sequencing.

Time: 3 years

Description: FFPE samples retrieved from patients genotyped with MET-N375S polymorphism will be subjected to MET and HER2 testing Abbott PathVysion DNA test kits. Data will be analysed with fluorescence microscopy. HER2 amplification will be defined as gene copies versus chromosome 17 polysomy. MET amplification will be defined as gene copies per nucleus.

Measure: Presence of MET and HER2 amplification using fluorescence in situ hybridization (FISH)

Time: 3 years

Description: PLA will be performed using DUOLINK in situ hybridization. Validation MET and HER2 antibodies will be used for the assay, and signal will be detected with fluorescence microscopy. Detection and quantification of positive signals will determine the presence of MET-HER2 interaction in clinical specimens.

Measure: Interaction of cMet and HER2 receptor tyrosine kinases using proximity ligation assay (PLA)

Time: 3 years

2 Evaluating Mutations in MET and TP53 Among Patients Diagnosed With Squamous Cell Carcinoma

This study focuses on advanced lung and head and neck SCC tumours, with adjacent normal lung tissues. Biopsies will be performed in National University Health System, Singapore (NUHS) as part of participants' standard care. Patient blood was also required for extraction of cell free DNA (cfDNA) and genomic DNA (gDNA). Patients' medical records will also be reviewed for the purpose of this study.

NCT03938012
Conditions
  1. Squamous Cell Carcinoma of the Lung
  2. Squamous Cell Carcinoma of the Head and Neck
MeSH:Carcinoma Carcinoma, Squamous Cell Squamous Cell Carcinoma of Head and Neck Lung Neoplasms
HPO:Carcinoma Neoplasm of the lung Squamous cell carcinoma

Customised probes detecting wildtype MET allele or MET-N375S allele are designed to for genotyping (homozygous/heterozygous).. Identification of TP53 mutation using Sanger sequencing. --- N375S ---

FFPE samples retrieved from patients genotyped with MET-N375S polymorphism will be subjected to MET and HER2 testing Abbott PathVysion DNA test kits. --- N375S ---

Primary Outcomes

Description: Germline DNA from the patients will be harvested from whole blood, and the polymorphic MET variant will be determined using ddPCR. Customised probes detecting wildtype MET allele or MET-N375S allele are designed to for genotyping (homozygous/heterozygous).

Measure: Identification of MET mutation using digital droplet PCR (ddPCR)

Time: 2 years

Description: DNA from the tumour specimens will be harvested for sequencing to identify cases with somatic mutations of TP53 gene. Changes in codon sequences will be reported.

Measure: Identification of TP53 mutation using Sanger sequencing

Time: 2 years

Description: FFPE samples retrieved from patients genotyped with MET-N375S polymorphism will be subjected to MET and HER2 testing Abbott PathVysion DNA test kits. Data will be analysed with fluorescence microscopy. HER2 amplification will be defined as gene copies versus chromosome 17 polysomy. MET amplification will be defined as gene copies per nucleus.

Measure: Presence of MET and HER2 amplification using fluorescence in situ hybridization (FISH)

Time: 2 years

Description: PLA will be performed using DUOLINK in situ hybridization. Validation MET and HER2 antibodies will be used for the assay, and signal will be detected with fluorescence microscopy. Detection and quantification of positive signals will determine the presence of MET-HER2 interaction in clinical specimens.

Measure: Interaction of MET and HER2 receptor tyrosine kinases using proximity ligation assay (PLA)

Time: 2 years

Description: Extracted cfDNA will be subjected to ddPCR using designed probes for MET and TP53 mutations. Copies of cfDNA/1mL of plasma will be reported.

Measure: Cell free DNA (cfDNA) will be extracted from patients' plasma to detect for presence of somatic/germline mutation

Time: 2 years


HPO Nodes