Lynch Syndrome Can be Diagnosed Just From Somatic Mismatch Repair Mutation

NCT04516083 | Unknown DMC

• 1 other identifier: 1272883
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cancer Gene Mutation; Lynch Syndrome; Endometrial Cancer; Somatic Mutation

Outcome Measures

Primary Outcomes (1)

• Number of patients who have a somatic mutation at the same time as a germline mutation

  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.

  Through study completion, an average of 18 months

Interventions

Mismatch repair instability somatic and germline testing DIAGNOSTIC_TEST

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.

Eligibility Criteria

• Gender Eligibility Details: Female as this is endometrial carcinoma
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The population includes female patients of all ages and races who are from a low socioeconomic background defined by the american psychological association. These females usually reside in underserved area. All the patients are diagnosed with endometrial endometrioid adenocarcinoma via tissue biopsy.

You may qualify if:

• Underserved areas. Diagnosis of endometrial endometrioid carcinoma. Low socioeconomic status. Positive mismatch repair staining. All races. All ages. All cancer grades. All cancer stages .

You may not qualify if:

• Diagnosis of type 2 endometrial carcinoma. Cancer diagnosis other than Endometrial. No mismatch repair genes mutation. High socioeconomic status.

Sponsors & Collaborators

• RWJ Barnabas Health at Jersey City Medical Center: lead

Study Sites (1)

Jersey city medical center

Jersey City, New Jersey, 07302, United States

RECRUITING

Related Publications (3)

• Chu MM, Liu SS, Tam KF, Ip PP, Cheung AN, Ngan HY. The Significance of Mismatch Repair Deficiency in Young Patients With Endometrial Cancer. Int J Gynecol Pathol. 2015 Sep;34(5):403-10. doi: 10.1097/PGP.0000000000000174.

  PMID: 26262451 BACKGROUND

• Modica I, Soslow RA, Black D, Tornos C, Kauff N, Shia J. Utility of immunohistochemistry in predicting microsatellite instability in endometrial carcinoma. Am J Surg Pathol. 2007 May;31(5):744-51. doi: 10.1097/01.pas.0000213428.61374.06.

  PMID: 17460459 BACKGROUND

• Kahn RM, Gordhandas S, Maddy BP, Baltich Nelson B, Askin G, Christos PJ, Caputo TA, Chapman-Davis E, Holcomb K, Frey MK. Universal endometrial cancer tumor typing: How much has immunohistochemistry, microsatellite instability, and MLH1 methylation improved the diagnosis of Lynch syndrome across the population? Cancer. 2019 Sep 15;125(18):3172-3183. doi: 10.1002/cncr.32203. Epub 2019 May 31.

  PMID: 31150123 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms, Hereditary Nonpolyposis; Endometrial Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Central Study Contacts

Ariel Polonsky, MD

CONTACT

5512276993; arielpolonskymd@gmail.com

Noah Goldman, MD

CONTACT

ng510@njms.rutgers.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2020
• First Posted: August 17, 2020
• Study Start: December 21, 2019
• Primary Completion: December 30, 2020
• Study Completion: June 30, 2021
• Last Updated: August 18, 2020

Record last verified: 2020-08

Locations

US (1)