Short Tandem Repeat (STR) Analysis Identifies a Cancer Transmitted from an Organ Donor to 4 Transplant Recipients
M. Park1, J. Van Ziffle1, E. Collisson1, J. Grenert1, S. Behr1, A. Gonzalez1, J. Chou1, S. Maisel1, T. Friedlander1, C. Freise1, J. Shoji1, T. Semrad2, P. Chin-Hong1, C. Atreya1
1UCSF, San Francisco, CA, 2Gene Upshaw Memorial Tahoe Forest Cancer Center, Truckee, CA
Meeting: 2020 American Transplant Congress
Abstract number: D-018
Keywords: Donors, marginal, Donors, unrelated, Informed consent, Post-transplant malignancy
Session Information
Session Name: Poster Session D: Kidney Deceased Donor Selection
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: Organ donors are systematically screened for infection, while screening for malignancy is less rigorous. The true incidence of donor-transmitted malignancies is unknown due to lack of universal tumor testing post-transplant. We describe the transmission of a gastrointestinal (GI) adenocarcinoma from one donor to four transplant recipients. The donor was a 34-year-old overweight, nonverbal man living in a group home with no prior h/o malignancy. Cause of death was recorded as anoxia due to cardiac arrest attributed to polypharmacy. Four recipients received his organs (Table 1); all developed adenocarcinoma.
*Methods: IRB approval for chart review was obtained. Records pertaining to the Donor and Heart Recipient (deceased) were obtained from the UNOS OPTN online database, UNet. The other 3 organ recipients provided individual research consent for chart review and molecular profiling. Short Tandem Repeat (STR) genotyping of each recipient’s tumors was performed using the AmpFlSTR Identifiler Kit, followed by capillary electrophoresis. Tumor and germline DNA were subjected to next generation sequencing (NGS) of 479 genes.
*Results: Donor origin was established by STR analysis, with tumors showing high levels of donor alleles. In the Liver and Right KP recipients, 15 of 15 STR loci were amplified by PCR, with tumors showing high levels of donor alleles in 13 and 14 loci. Human Leukocyte Antigen (HLA) typing and NGS also demonstrated that tumors in the Left Kidney Recipient and the Right KP Recipient were donor-transmitted. Tumors from the Liver, Left Kidney, and Right KP Recipients were all poorly differentiated adenocarcinoma with signet ring features and stained positive for markers consistent with a GI primary, while markers for melanoma, breast, lung, and gynecologic cancers were negative. Based on the immunohistochemical profile and NGS data, the stomach was considered the most probable organ of origin.
*Conclusions: To improve patient safety, Short Tandem Repeat (STR) testing should be standard immediately upon diagnosis of cancer in any organ transplant recipient. Utilization of new screening methods of organ donors for malignancy may also be warranted. While other methods can be used for molecular identity testing (e.g., HLA typing and NGS described here), STR analysis is cost and time efficient, with easily interpretable results. One patient remains alive and without evidence of cancer following prompt organ explant.
Heart | Liver | Left kidney | Right kidney-pancreas (KP) | |
Description | 69 yo man; ischemic cardiomyopathy | 54 yo man; alcoholic cirrhosis | 63 yo man; multifocal urothelial carcinoma in situ, s/p bilateral nephroureterectomy | 41 yo woman; type 1 diabetes mellitus |
Vital status | Died post-transplant day (PTD) 143 | Died PTD 293 | Died PTD 812 | Alive |
To cite this abstract in AMA style:
Park M, Ziffle JVan, Collisson E, Grenert J, Behr S, Gonzalez A, Chou J, Maisel S, Friedlander T, Freise C, Shoji J, Semrad T, Chin-Hong P, Atreya C. Short Tandem Repeat (STR) Analysis Identifies a Cancer Transmitted from an Organ Donor to 4 Transplant Recipients [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/short-tandem-repeat-str-analysis-identifies-a-cancer-transmitted-from-an-organ-donor-to-4-transplant-recipients/. Accessed November 22, 2024.« Back to 2020 American Transplant Congress