Potential participants may be identified through the following sources: patients who will undergo or are currently undergoing clinical evaluation in practices such as, but not limited to, hematology-oncology, gastroenterology-hepatology, radiation-oncology and surgery. Participants will be enrolled in the study indefinitely unless a request to withdraw is made.

Participants will be scheduled to review the study specifics, review consent and gather medical information. Once consented, samples will be collected. When the samples are received by Exact Sciences, DNA and RNA will be extracted, and sequencing will be performed. Following pan-genomic testing, participants will receive the full report with results from their care team and results will also be added to the patient's portal. If a germline finding is identified (positive pathogenic variant) the participant will also be referred for a genetic counselor visit. All results from the germline hereditary test will be reviewed by a certified genetic counselor in addition to a review of their pedigree. To help with review of any genetic research findings, the study team may request to obtain genomic data from previous genetic testing (clinical or research based).

Pan-genomic Testing

Clinical Trials Referral Office

Katie M. Gano, M.S.

Jewel J. Samadder, M.D.

Jeremy C. Jones, M.D.

Mrinal S. Patnaik, M.B.B.S.

The purpose of this study is to evaluate the integration of cancer pan-genetic testing into a cancer clinical practice and understand both its use and effect in "real world" practice conditions.

Each participant will have residual/archived tissue and a new blood (or saliva, hair follicle) sample for pan-genomic testing as per standard of care testing. Additional samples (including but not limited to tissue, bone marrow, blood, urine, stool, hair follicles, etc) may be requested/collected to be used for additional genomic and other omics studies.

INTERogating Cancer for Etiology, Prevention and Therapy Navigation

INTERogating Cancer for Etiology, Prevention and Therapy Navigation (INTERCEPTioN)

Genomic sequencing of tumor tissue and blood will be performed to determine genomic alterations in germline and somatic cancer-related genes (SNVs, indels, CNVs from DNA and fusions from RNA) to allow the ordering hematologist/oncologist/provider to determine optimal therapy and clinical trial prospective. Researchers across the field of genomic sequencing report findings about new variations in scientific publications and collect it in databases every day. Consequently, any patient's variant of uncertain significance (VUS) result could be reclassified by emerging findings, turning previously unresolved tests into diagnostic answers. Our Translational Omics Program has a system to re-analyze a patient's exome/genome data against these new genetic findings-reviewing data and comparing it with emerging clinical genetic data to facilitate diagnoses.

Mayo Clinic

Principal Investigator

Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Syndrome

Adenocarcinoma

Endometrial Neoplasms

Colorectal Neoplasms

Colorectal Neoplasms, Hereditary Nonpolyposis

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Neoplastic Syndromes, Hereditary

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Genetic Diseases, Inborn

DNA Repair-Deficiency Disorders

Metabolic Diseases

Each Endometrial Endometrioid adenocarcinoma is routinely stained for MMR mutation to seek for tumor genetic instability. If stains positive, the patient is called in for genetic blood testing to look for the same mutation in the germline.

Mismatch repair instability somatic and germline testing

Ariel Polonsky, MD

Noah Goldman, MD

The objective of the study is the provide proof of high correlation between somatic and germline mismatch repair instability. This correlation is specifically researched in an area where patients have less access to cancer education and genetic testing for various reasons such as lack of insurance and general accessibility.

The study concentrates on early diagnosis of Lynch syndrome. Lynch syndrome is usually diagnosed from a blood test resulting in a mutation of one of the mismatch repair genes. Those are MLH1, MSH2, MSH 6, PMS2. A mutation in one of these genes creates a mismatch repair instability,hence higher incidence of cancers in specific organ groups. Amongst these organs are the Uterus, Ovaries, Upper genitourinary system, Pancreas and GI system.

The most common endometrial carcinoma which is found in Lynch syndrome is of endometrioid histology. Most patients with known germline mismatch repair instability, have the same somatic mutation. Our study is looking into correlating somatic mutation to germline mutation.

By doing so, patients diagnosed with somatic mismatch repair instability will be also diagnosed with lynch syndrome without germline genetic testing.

Screening programs will be utilized earlier and preventive procedures offered.

Due to less access to educational programs, genetic counseling and testing in underserved areas, patients are sometimes lost to follow up. Our study seeks to prove high correlation between somatic and germline mutations and by doing so, patient will be diagnosed with Lynch syndrome straight after endometrial cancer staging. As a result, increased compliance will be expected and patients will be offered the recommended preventative surgeries and screening protocols.

Lynch Syndrome Can be Diagnosed Just From Somatic Mismatch Repair Mutation

Correlation Between Somatic Mismatch Repair Instability and Germline Mismatch Repair Instability, in Low Socioeconomic Background Population Diagnosed With Endometrial Endometrioid Adenocarcinoma

1. Resected tissue during endometrial staging will be immunohistochemically stained for MMR mutation.
2. Patient blood test will be checked for MMR gene mutation
3. Linear regression curve will be constructed to evaluate the correlation between somatic and germline mutation.

RWJ Barnabas Health at Jersey City Medical Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
INTERogating Cancer for Etiology, Prevention and Therapy Navigation	NCT06008392	Cancer Cancer Gene Mut... PAN Gene Mutati...	Pan-genomic Tes...	18 Years -	Mayo Clinic
Lynch Syndrome Can be Diagnosed Just From Somatic Mismatch Repair Mutation	NCT04516083	Cancer Gene Mut... Lynch Syndrome Endometrial Can... Somatic Mutatio...	Mismatch repair...	-	RWJ Barnabas Health at Jersey City Medical Center
INTERogating Cancer for Etiology, Prevention and Therapy Navigation	NCT06008392	Cancer Cancer Gene Mut... PAN Gene Mutati...	Pan-genomic Tes...	18 Years -	Mayo Clinic

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