Hereditary leiomyomatosis and RCC syndrome-associated renal cancer is related to
germline mutation of the fumarate hydratase (FH) gene.
(21) 100 patients with endometrial cancer diagnosed <50 years of age MMR
germline mutation Anagnostopoulos 35 patients with endometrial cancer et al.
Even in patients with apparently sporadic PCCs, up to 25% will have unsuspected
germline mutations. Younger age and multifocal tumors, as in our patients, are significantly associated with the presence of a mutation.
Mutations that occur in the formation of gametes are called
germline mutations because they are inherited and can be predicted.
Formal documentation of a
germline mutation, however, requires genetic testing of blood DNA.
SMARCB1 mutations can arise de novo or be secondary to a
germline mutation, which should prompt genetic counseling [9].
Genetic testing is of paramount importance in pediatric patients with an apparently sporadic PHEO, because (1) the rate of mutations found in this clinical setting is close to 80.0%; (2) 10 PHEO-associated genes have been reported in pediatric patients, each gene conferring distinct profiles of propensity for the development of chromaffin and nonchromaffin cell tumors and for biological behaviors; and (3) it allows for tailoring specific diagnostic, treatment, and surveillance programs to these patients, taking into account the
germline mutation founded and its genotype-phenotype correlation [5, 22, 23, 30-33, 50, 118].
[17] NCI, NCI Dictionary of Cancer Terms,
germline mutation, Secondary NCI Dictionary of Cancer Terms, "
germline mutation", https://www.cancer.gov/publications/dictionaries/ cancer-terms?cdrid=46384, 2017.
For kindred families fulfilling the Amsterdam criteria, the chance of identifying a
germline mutation is 40% to 50% [11].
It is already known that around 1% of PCC patients were negative for mutations in the other known susceptibility genes carried a
germline mutation affecting MAX [26, 27].
Von Hippel-Lindau disease is a hereditary cancer syndrome caused by a
germline mutation in or deletion of the VHL gene, and patients are at risk for developing tumors and fluid-filled sacs (cysts) in a number of organs.
MSI thereby serves as a reliable phenotypic marker of MMR deficiency in order to preselect patients eligible for
germline mutation analysis in the MMR genes [19].
