Genomic Profiling in Cancer Patients

Overview

The purpose of this study is to determine whether certain genes in cancer may be abnormal. When a gene is abnormal this is called a mutation. Most mutations in cancer cells are not inherited (passed down from parents) but happen after birth in the cancer itself. Most cancers have many mutations. Some of these mutations are important for the cancer cells to survive while others are not. The goal of this study is test cancer for certain mutations using leftover tumor tissue from a previous surgery or biopsy. Participants will also be asked to provide a tube of blood cheek (also known as a buccal) swab, or a saliva sample that contains normal genes for comparison. The purpose of Part B of this study is to: Understand how genetic changes in tumor effect the chance of responding to experimental cancer treatment. Understand how the genes in the tumor change overtime in response to targeted cancer treatment.

Interventions

• Genetic molecular profiling of tumors
  Part A is the molecular profiling of tumors. No new tumor biopsies will be performed in the context of Part A. If a pt does have a surgery or tumor biopsy , leftover tissue (or an additional core) from this procedure may be used for molecular profiling. Clinical Assay(s): This testing will be performed in the CLIA-certified Molecular Diagnostics Service laboratory. Research Assay(s): This protocol will also be used as a platform to pilot the use of investigational "next-generation" profiling tec
• Genetic Clinical Germline Analysis
  Part C: Clinical Germline Analysis Participants who have donated a matched normal peripheral blood sample for comparison to somatic sequence will be offered the opportunity to have that germline DNA sample analyzed for the presence of deleterious or likely deleterious mutations in genes on the MSK-IMPACT panel that are known to be linked to inherited susceptibility or that are included on consensus lists of genes that should undergo secondary analysis (e.g. the "ACMG list"). Part D: Germline Pr

Primary outcome measures

• frequency of "actionable" oncogenic mutations [Time frame: 1 year]

Secondary outcome measures (3)

• To determine the impact of molecular profiling results performed in the CLIA-setting on the treatment of patients. [Time frame: 1 year]
• interrogate the mechanisms [Time frame: 1 year]
• To explore the genetic mechanisms of tumorigenesis [Time frame: 2]

Eligibility criteria

Inclusion criteria

Part A:

• Patients with a history of cancer or patients without a documented cancer history undergoing a surgical procedure, endoscopy, biopsy, or liquid biopsy (for example cell free DNA testing) to confirm or exclude a cancer diagnosis, or
• Any participant having a test or procedure that has the potential to provide a specimen that can be banked for future research purposes, or
• Any participant who has already had a diagnostic or therapeutic procedure that has yielded tissue, blood or other bodily fluids presently in the archive but who has not yet been approached to participate is also eligible.

Part B:

• Patients must be successfully registered to Part A of MSKCC IRB# 12-245
• Prior written approval for patient consent obtained from the Principal/Co-Principal Investigator of MSKCC IRB # 12-245.

Part C:

• Patient must be receiving ongoing care at MSK or a CHERPn/ Alliance/Affiliate site or have previously consulted with an MSK physician.
• Patient must have successfully consented to Part A of this study.

Part D:

• Patients with no personal cancer history at increased risk for cancer development due to family history, molecular cancer marker, know carrier status of a gene associated with increased cancer risk or prior/ongoing environmental exposures or lifestyle factors.

Exclusion criteria

All Parts:

• Unwilling or unable to provide informed consent.

Part C:

• All patients consenting to Part A are eligible to consent to 12-245, Part C. Most patients will be eligible to receive clinical germline testing with return of results to the patient/health care providers. However, several exclusion criteria apply and are outlined below

• Solid tumor patients: Secondary germline analysis using BAM files generated for MSK-IMPACT testing is not an option for patients with solid tumors and an acute or chronic hematologic neoplasm that would preclude the use of blood or saliva as a source of germline DNA. Such patient may be eligible for primary germline testing using a non-blood source of germline DNA as per standard clinical guidelines. Solid tumor patients who have had an allogenic bone marrow/stem cell transplant will only be considered eligible for germline testing under Part C if a sample adequate for germline testing had previously been collected prior to allogenic bone marrow/stem cell transplant.
• Hematologic cancer patients: For patients with a hematopoietic neoplasm, germline testing may be an option under Part C using nail clippings or another non-blood source of DNA as per standard clinical practice. For patients who have had an allogenic bone marrow/stem cell transplant, clinical germline testing will only be considered under Part C if a sample adequate for germline testing had previously been collected prior to Allogenic bone marrow/stem cell transplant.

Part D

• Exclusion criteria are same as those for Part C outlined above.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 18 centers

• St. Vincent (Data Collection Only) — Bridgeport
• Hartford Healthcare Cancer Institute @ Hartford Hospital — Hartford
• Norwalk Hospital — Norwalk
• Baptist Alliance MCI — Miami
• Memorial Sloan Kettering Basking Ridge — Basking Ridge
• Memorial Sloan Kettering Monmouth — Middletown
• Memorial Sloan Kettering Bergen — Montvale
• Kings County Hopsital Center — Brooklyn
• … and 10 more centers

Publications

• Borio M, Sheehan M, Katabi N, Sacca RE, Maio A, Kemel Y, Khurram A, Mandelker D, Birsoy O, Solit D, Carlo MI, Liu Y, Abbass M, Banaszak L, Kesserwan C, Murciano-Goroff YR, Latham A, Offit K, Wong RJ, Ghossein R, Boucai L, Tuttle M, Stadler ZK. Prevalence of Germline Pathogenic RET Variants in a Pan-Cancer Patient Population. JCO Precis Oncol. 2026 May;10(5):e2500737. doi: 10.1200/PO-25-00737. Epub PMID 42172561
• Gelfer R, Gulla A, Kalvin HL, Song Y, Harding J, Abou-Alfa GK, O'Reilly EM, Park W, Chandwani R, Wei A, Kingham P, Drebin J, Balachandran V, D'Angelica M, Soares K, Gonen M, Jarnagin WR. KRAS Variants Are Associated With Survival Outcomes and Genomic Alterations in Biliary Tract Cancers. JCO Precis Oncol. 2024 Dec;8:e2400263. doi: 10.1200/PO.24.00263. Epub 2024 Dec 6. PMID 39642327
• Mondaca S, Walch H, Sepulveda S, Schultz N, Munoz G, Yaqubie A, Macanas P, Pareja C, Garcia P, Chatila W, Nervi B, Li B, Harding JJ, Viviani P, Roa JC, Abou-Alfa GK. Clinical and Genomic Characterization of ERBB2-Altered Gallbladder Cancer: Exploring Differences Between an American and a Chilean Cohort. JCO Glob Oncol. 2024 Oct;10:e2400090. doi: 10.1200/GO.24.00090. Epub 2024 Oct 10. PMID 39388662
• Seldon CS, Meiyappan K, Hoffman H, Guo JA, Goel N, Hwang WL, Nguyen PL, Mahal BA, Alshalalfa M. Genomic alterations predictive of poor clinical outcomes in pan-cancer. Oncotarget. 2022 Sep 28;13:1069-1077. doi: 10.18632/oncotarget.28276. eCollection 2022. PMID 36187555
• Rosenzweig J, Pillai PM, Prockop S, Benayed R, Eidenschink Brodersen L, Najfeld V, Loken MR, Zhang Y, Shukla N. Acute myeloid leukemia with an MN1-ETV6 fusion in a young child with Down syndrome. Cold Spring Harb Mol Case Stud. 2022 Apr 28;8(3):a006167. doi: 10.1101/mcs.a006167. Print 2022 Apr. PMID 35483876
• Lin AL, Tabar V, Young RJ, Cohen M, Cuaron J, Yang TJ, Rosenblum M, Rudneva VA, Geer EB, Bodei L. Synergism of Checkpoint Inhibitors and Peptide Receptor Radionuclide Therapy in the Treatment of Pituitary Carcinoma. J Endocr Soc. 2021 Aug 7;5(10):bvab133. doi: 10.1210/jendso/bvab133. eCollection 2021 Oct 1. PMID 34466766
• Fiala EM, Jayakumaran G, Mauguen A, Kennedy JA, Bouvier N, Kemel Y, Fleischut MH, Maio A, Salo-Mullen EE, Sheehan M, Arnold AG, Latham A, Carlo MI, Cadoo K, Murkherjee S, Slotkin EK, Trippett T, Glade Bender J, Meyers PA, Wexler L, Dela Cruz FS, Cheung NK, Basu E, Kentsis A, Ortiz M, Francis JH, Dunkel IJ, Khakoo Y, Gilheeney S, Farouk Sait S, Forlenza CJ, Sulis M, Karajannis M, Modak S, Gerstle J PMID 34308366
• Stadler ZK, Maio A, Chakravarty D, Kemel Y, Sheehan M, Salo-Mullen E, Tkachuk K, Fong CJ, Nguyen B, Erakky A, Cadoo K, Liu Y, Carlo MI, Latham A, Zhang H, Kundra R, Smith S, Galle J, Aghajanian C, Abu-Rustum N, Varghese A, O'Reilly EM, Morris M, Abida W, Walsh M, Drilon A, Jayakumaran G, Zehir A, Ladanyi M, Ceyhan-Birsoy O, Solit DB, Schultz N, Berger MF, Mandelker D, Diaz LA Jr, Offit K, Robson M PMID 34133209

Identifiers

NCT: NCT01775072 · 12-245

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗