IDH1 mutated low grade astrocytoma occurring in MSH2 mutated Lynch syndrome family

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Lynch syndrome (LS) is an autosomal dominant tumour predisposition syndrome caused by a germline mutation in one of the DNA mismatch repair (MMR) genes. Patients with these mutations have an increased risk of brain tumours, the vast majority of which are glioblastomas and medulloblastomas, and their occurrence has been termed Turcot Syndrome. The case presented herein of a member of a Lynch syndrome family with an MSH2 mutation expands the spectrum of brain tumours occurring in Lynch syndrome to include low grade astrocytomas,
and is the first reported case of an IDH1 (R132H) mutated brain tumour occurring in a Lynch syndrome family.

 Patients with a pathogenic DNA MMR gene mutation have a 10–50% risk for developing colorectal carcinoma at an early age (mean 45–50 years) and extracolonic malignancies can occur including endometrial, ovarian, hepatic, pancreatic and ureteric carcinomas and brain tumours [1] and [2]. Although the 1–3% lifetime risk of brain tumours is low compared to other extracolonic tumours in LS families [1], this risk is 6 fold that of the general population and its occurrence has been termed Turcot Syndrome. The brain tumours previously described in Lynch/Turcot syndrome have mostly been high grade gliomas, predominantly glioblastomas, and less commonly, medulloblastomas [1], [3], [4], [5] and [6]. A recent European study described the risk of developing brain tumours being highest (2.5%) in Lynch syndrome patients with MSH2 mutations, contained the first description of low grade astrocytoma in Lynch syndrome (1/47 gliomas was a pilocytic astrocytoma (WHO grade I), and 1/47 was a diffuse astrocytoma (WHO grade II)), and showed universal negativity for mIDH1 immunoreactivity in Lynch syndrome associated glioma [7].The present case adds to the sparse literature on low grade astrocytomas in Lynch syndrome and is the first report of a Lynch syndrome associated IDH1 R132H mutated glioma....

 

4. Discussion

There are two unique aspects to our case.First, low grade astrocytoma histology has only rarely been previously reported in LS families [6] and [7].Second, to our knowledge, this is the first case of IDH1 mutated glioma reported in the setting of an LS family [8] and [9].Whether the presence of a mutated IDH1 glioma in a patient with MSH2 mutation is a chance occurrence or is informative about oncogenesis remains uncertain.

5. Conclusion

Brain tumours reported in Lynch syndrome families have predominantly been glioblastoma or medulloblastoma, and the present case expands this spectrum to include mIDH1 (R132H) mutated low grade astrocytoma.