A tumor profile in Patau syndrome (trisomy 13)

Abstract

Individuals with trisomic conditions like Down syndrome and Edwards syndrome are prone to certain types of malignancy. However, for Patau syndrome (constitutional trisomy 13), which occurs in 1/10,000-1/20,000 live births, the tumor profile has not been well characterized. An awareness of susceptibility to malignancies can improve care of affected individuals, as well as further our understanding of the contribution of trisomy to carcinogenesis. Therefore, we conducted an extensive review of the literature; we found 17 malignancies reported in individuals with Patau syndrome. These comprised eight embryonic tumors, three leukemias, two malignant germ cell tumors, two carcinomas, a malignant brain tumor, and a sarcoma. Benign tumors were mainly extragonadal teratomas. The small number of reported malignant tumors suggests that there is not an increased risk of cancer in the context of trisomy 13. The tumor profile in Patau syndrome differs from that observed in Edwards syndrome (trisomy 18) and Down syndrome (trisomy 21), suggesting that the supernumerary chromosome 13 could promote particular tumor formations as it does particular malformations. No general and direct relationships of tumor occurrence with organ weight, congenital malformations, histological changes, or presence of tumor suppressor genes on chromosome 13 were observed. However, some tumors were found in tissues whose growth and development are controlled by genes mapping to chromosome 13. Recent reports of successful outcomes following surgical treatment and adapted chemotherapy indicate that treatment of cancer is possible in Patau syndrome.

Integrating the DNA damage and protein stress responses during cancer development and treatment

“…Although aneuploidy is evident in these mice, malignant transformation is a rare and late event , questioning whether aneuploidy as such is causative for cancer development . Differences in cancer incidence among individuals with identical aneuploidy, as well as between common genetic disorders such as trisomies 13 , 18 and 21 , suggest that additional hits are required for cancer to evolve. Moreover, extensive analysis in common sporadic cancers with aneuploidy demonstrated the low frequency of mutations in caretaker genes*, including SAC genes, arguing against their role in promoting cancer .…”

“…Particular attention should be given to the p16 INK4A –Rb–E2F pathway, which is a major ‘molecular crossroad’ that most mitogenic/oncogenic signals converge to. Its phosphorylation status determines whether the cell will bypass the ‘restriction point’ of G 1 phase, committing the cell to progress to S phase without the requirement for extracellular stimulants …”

Prenatal Sacrococcygeal Teratoma Diagnosed in a Fetus with Partial Trisomy 13q22

“…Additionally, an intraoral teratoma was seen in a 24 week-old fetus with Trisomy 13. The umbilical cord of a 17-week-old fetus with Trisomy 13 was also found to have a teratoma [6].…”

“…Other than germ cell tumors, leukemia, cutaneous tumors, carcinomas, adenomas, and cerebral tumors have been reported in association with Trisomy 13. However, most of these were diagnosed postnatally [6].…”

Adenocarcinoma and polyposis of the colon in a 20-year-old patient with Trisomy 13: a case report

“…Increased incidence of malignancy in patients with constitutional Trisomy, including Trisomy 13, 18, and 21, has been described previously. Specifically for Trisomy 13, a recent review found 17 malignant tumors reported in the literature [ 6 ]. The most common reported malignancies include embryonic tumors, predominantly neuroblastoma and nephroblastoma, followed by malignant germ cell tumors, leukemias, brain cancer, carcinomas, and sarcomas.…”