SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03938012

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

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 Squamous Cell Carcinoma of the Lung 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


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

Time Perspective: Prospective

Case-Only


There is one SNP

SNPs


1 N375S

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 ---



HPO Nodes


HPO:
Carcinoma
Genes 11
PTEN CDKN1B APC MLH1 MSH2 FGFR3 KIT DKC1 RSPO1 STK11 NLRP1
Neoplasm of the lung
Genes 43
WT1 KRAS SLC22A18 STK11 IRF1 AKT1 C11ORF95 PRKN PPP2R1B ERBB2 TRPV3 TSC1 POU6F2 TSC2 EWSR1 RELA KEAP1 REST DIS3L2 SFTPA2 GPC3 MBTPS2 LMNA PTEN BRAF BRCA2 EGFR RB1 TRIP13 PDGFRB TERT SFTPC PIK3CA TRIM28 DICER1 MAP3K8 HPGD SLCO2A1 H19 TP53 NOTCH3 BAP1 WRN
Squamous cell carcinoma
Genes 62
BLM TYR CDKN2A NUTM1 TGFBR2 KRT5 COL7A1 GTF2E2 GJB2 ERCC2 KRT14 ERCC3 CIB1 ERCC4 ERCC5 WWOX LMNA SASH1 RNF6 TINF2 ING1 SLC17A9 DOCK8 LZTS1 PSENEN FDPS NTHL1 CTSC GJB6 BRD4 POLH RECQL4 RNF113A TMC6 FERMT1 MC1R WRN TMC8 LAMA3 MPLKIP GTF2H5 WNT10A DKC1 LAMB3 NLRP1 LAMC2 SLC45A2 OCA2 XPC MMP1 TNFRSF10B DCC WRAP53 TERC TERT RSPO1 DDB2 SLX4 STAT1 MVD IL7 MVK