Germline sequencing identifies rare variants in finnish subjects with familial germ cell tumors

Erin L. Crowgey, Tea Soini, Nidhi Shah, Satu Liisa Pauniaho, Pekka Lahdenne, David B. Wilson, Markku Heikinheimo, Todd E. Druley

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Pediatric germ cell tumors are rare, representing about 3% of childhood malig-nancies in children less than 15 years of age, presenting in neonates or adolescents with a greater incidence noted in older adolescents. Aberrations in primordial germ cell prolifera-tion/differentiation can lead to a variety of neoplasms, including teratomas, embryonal carcinoma, choriocarcinoma, and yolk sac tumors. Patients and Methods: Three Finnish families with varying familial germ cell tumors were identified, and whole-genome sequencing was performed using an Illumina sequencing platform. In total, 22 unique subjects across the three families were sequenced. Family 1 proband (female) was affected by malignant ovarian teratoma, Family 2 proband (female) was affected by sacrococcygeal teratoma with yolk sac tumor in the setting of Cornelia de Lange syndrome, and Family 3 proband (male) was affected by malignant testicular tera-toma. Rare variants were identified using an autosomal recessive or de novo model of inheritance. Results: For family 1 proband (female), an autosomal recessive or de novo model of inheritance identified variants of interest in the following genes: CD109, IKBKB, and CTNNA3, SUPT6H, MUC5AC, and FRG1. Family 2 proband (female) analysis identified gene variants of interest in the following genes: LONRF2, ANO7, HS6ST1, PRB2, and DNM2. Family 3 proband (male) analysis identified the following potential genes: CRIPAK, KRTAP5-7, and CACNA1B. Conclusion: Leveraging deep pedigrees and next-generation sequencing, rare germline variants were identified that were enriched in three families from Finland with a history of familial germ cell tumors. The data presented support the importance of germline mutations when analyzing complex cancers with a low somatic mutation landscape.

Original languageEnglish
Pages (from-to)127-137
Number of pages11
JournalApplication of Clinical Genetics
Volume13
DOIs
StatePublished - 2020

Keywords

  • Familial germ cell tumors
  • Genomics
  • Germline analysis
  • Next generation sequencing

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