Rare Case of a Turner Syndrome Patient with Metastatic Dysgerminoma and No Y-Chromosomal Material with Pathogenic Variants Found in KIT and MTOR

TY - JOUR

T1 - Rare Case of a Turner Syndrome Patient with Metastatic Dysgerminoma and No Y-Chromosomal Material with Pathogenic Variants Found in KIT and MTOR

AU - Balle, Camilla Mains

AU - Kassentoft, Christine Gaasdal

AU - Van Heusden, Jolinda Iris

AU - Knudsen, Michael

AU - Raaby, Line

AU - Gravholt, Claus Højbjerg

N1 - Publisher Copyright: © 2024 S. Karger AG, Basel.

PY - 2024/7/1

Y1 - 2024/7/1

N2 - Introduction: The presence of Y-chromosomal material in females with Turner syndrome (TS) is a well-established risk factor for developing gonadoblastoma and malignant transformations thereof. However, these events are rarely seen in TS patients with no Y-chromosomal material. Thus, it is the current understanding that parts of the Y-chromosome are essential for the malignant transformation of gonadoblastoma in the dysgenetic gonad. Methods: We report a case of a TS female with an apparent 46,X,idic(Xq) karyotype, who was diagnosed with a metastatic dysgerminoma. Whole exome sequencing of the tumor and blood, along with RNA sequencing of the tumor, was performed to comprehensively search for cryptic Y-chromosomal material and pathogenic variants. Results: No Y-chromosomal material was detected in either tumor or blood. Whole exome-sequencing of DNA and RNA revealed a pathogenic somatic gain-of-function mutation in KIT and a pathogenic missense mutation in MTOR. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy, followed by adjuvant chemotherapy. Unfortunately, she died due to chemotherapy-induced pneumonitis 7 months after the initial diagnosis. Conclusion: Females with TS can develop metastatic dysgerminoma even in the absence of Y-chromosomalmaterial. This questions the current understanding of Y-chromosomal material being essential for the malignant transformation of a gonadoblastoma in the dysgenetic gonad.

AB - Introduction: The presence of Y-chromosomal material in females with Turner syndrome (TS) is a well-established risk factor for developing gonadoblastoma and malignant transformations thereof. However, these events are rarely seen in TS patients with no Y-chromosomal material. Thus, it is the current understanding that parts of the Y-chromosome are essential for the malignant transformation of gonadoblastoma in the dysgenetic gonad. Methods: We report a case of a TS female with an apparent 46,X,idic(Xq) karyotype, who was diagnosed with a metastatic dysgerminoma. Whole exome sequencing of the tumor and blood, along with RNA sequencing of the tumor, was performed to comprehensively search for cryptic Y-chromosomal material and pathogenic variants. Results: No Y-chromosomal material was detected in either tumor or blood. Whole exome-sequencing of DNA and RNA revealed a pathogenic somatic gain-of-function mutation in KIT and a pathogenic missense mutation in MTOR. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy, followed by adjuvant chemotherapy. Unfortunately, she died due to chemotherapy-induced pneumonitis 7 months after the initial diagnosis. Conclusion: Females with TS can develop metastatic dysgerminoma even in the absence of Y-chromosomalmaterial. This questions the current understanding of Y-chromosomal material being essential for the malignant transformation of a gonadoblastoma in the dysgenetic gonad.

KW - Cancer

KW - Dysgerminoma

KW - Gonadoblastoma

KW - Turner syndrome

U2 - 10.1159/000536236

DO - 10.1159/000536236

M3 - Journal article

C2 - 38281483

AN - SCOPUS:85194738263

SN - 1661-5425

VL - 17

SP - 203

EP - 210

JO - Sexual Development

JF - Sexual Development

IS - 4-6

ER -