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Gastrointestinal Stromal Tumor in Monozygotic Twins Shows Distinct Mutational Status: A Case Report.

ABSTRACT: BACKGROUND Gastrointestinal stromal tumors (GISTs) are rare mesenchymal cancers that affect the gastrointestinal tract and are most often located in the stomach and proximal small intestine. The most common molecular genetic abnormalities underlying GIST carcinogenesis are mutations in the tyrosine kinase gene (KIT) and in the platelet-derived growth factor receptor alpha (PDGFRA) gene. To the best of our knowledge, no cases have been reported so far of synchronous diagnosis of GIST in 2 monozygotic twins presenting with clinical and morphological features of sporadic disease. CASE REPORT This report presents the cases of 2 monozygotic twin sisters who were diagnosed with GIST at the same age and who had different KIT exon 11 tumor mutational statuses. In the current report, the screening examination that led to early detection of GIST in one of the sisters was not motivated by any symptom, but by a GIST diagnosis in her twin a few days before. The literature was reviewed for pathological and molecular features associated with prognosis and treatment response. Furthermore, we identified identical genotypes of KIT and PDGFRA polymorphisms in the DNA of both tumors that might be present in the germline DNA. The present case supports the implementation of specific cancer screening in the context of monozygotic twins, regardless of identification of the genetic components involved. CONCLUSIONS Our report suggests that monozygotic twins with GIST can have different mutational statuses for KIT and PDGFRA. Referral for special screening should be considered for individuals who have a monozygotic twin diagnosed with cancer.

SUBMITTER: Sobral-Leite M

PROVIDER: S-EPMC7949489 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction: Nasopharyngeal carcinoma (NPC) is an epithelial tumor with high incidence in southern China and Southeast Asia. Oncogene mutation patterns in NPC have yet to be fully elucidated. It is also unclear if the inheritance of oncogene mutations contribute to the development of NPC. Using a multigene cancer exome sequencing panel, we sought to investigate oncogenes that were shared between both NPCs that developed in a pair of monozygotic female twins. We also examined these patterns, in the context of germline variants found in their unaffected brother. Case Summary: Twin A was first diagnosed with Stage I poorly differentiated NPC in 1988 and underwent radiation therapy with complete remission. Her cancer relapsed in 1991 as lung metastasis. She underwent left thoracotomy followed by systemic chemotherapy with cisplastin/5FU. In 2000, she had recurrence of cancer to her cervical lymph nodes again for which she received chemoradiation that resulted in complete remission. Her sister, Twin B was diagnosed with Stage I poorly differentiated NPC twenty years later (2008) and received radiation with complete remission. Both monozygotic twins were of southern Chinese ethnicity and had an unaffected brother. Methods: Archival formalin fixed paraffin embedded tumor tissue was retrieved from excision specimens of the two twins. A blood specimen was obtained from the unaffected brother. DNA was extracted and amplified using primer pairs targeted to 50 oncogenes selected by the Wellcome Trust Sanger Genomic Institute. Samples were barcoded and sequenced on a PGM™ semiconductor sequencer (Life Technologies, Foster City, CA). Results: Sequence of the twin NPCs identified similar mutations on KIT (1708A > C; M541L; rs3822214) and HRAS (269T > C; H27H; rs249860) with a closely related novel TP53 variants of 587G > A; R196Q and 567C > T; A189A between twin A and twin B, respectively. Both TP53 variants were located near the Zinc binding regions of the TP53 protein (P04637). The unaffected brother showed a similar HRAS mutation (269T > C; H27H; rs249860). All siblings possessed a complex inframe deletion on Exon 12 of PDGFRA (AGCCCAGATGGACATG; S566_E571delinsR; rs121913271). Conclusions: An intriguing relationship between these two twins affected by nasopharyngeal carcainoma was identified by multigene targeted exome sequencing. A possible inheritance pattern was also elucidated in their unaffected brother. This cluster of genes suggests a possible role for tyrosine kinase inhibitors as molecularly targeted therapies in NPC. Further analysis by tumor-normal comparisons may work toward confirming an effector pathway that could broaden our understanding of this aggressive tumor.

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Gastrointestinal Stromal Tumor in Monozygotic Twins Shows Distinct Mutational Status: A Case Report.

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