Abstract
BackgroundHereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare tumor predisposition syndrome characterized by cutaneous and uterine leiomyomas and papillary type 2 renal cell cancer. Germline mutation of the fumarate hydratase (FH) gene is known to be associated with HLRCC.Case presentationWe describe a 64-year-old father and his 39-year-old son with HLRCC who developed papillary type 2 RCCs lacking cutaneous leiomyomas at any site. A common missense mutation in the FH gene, (c.1021G > A, p.D341N) in exon 7, was detected in the 2 cases. Functional prediction with the bioinformatics programs, SIFT and Polyphen-2, reported “damaging (SIFT score 0.00)” and “probably damaging (PSIC score 1.621)” values, respectively. In 162 healthy individuals, there were no cases of a G transition to any base. Finally, (c.1021G > A) in exon 7, was identified as a point mutation.ConclusionWe report a family with HLRCC in which a novel missense mutation was detected. A familial papillary type 2 renal cancer should be considered HLRCC unless typical cutaneous leiomyomas do not occur.
Highlights
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare tumor predisposition syndrome characterized by cutaneous and uterine leiomyomas and papillary type 2 renal cell cancer
We report a family with HLRCC in which a novel missense mutation was detected
Clear cell RCC is the most common type, accounting for 70-80% of all RCCs, and VHL inactivation is very common in both sporadic clear cell RCC and the hereditary cancer syndrome known as von Hippel-Lindau disease [12]
Summary
Hereditary renal cell cancer comprises an estimated 35% of RCCs, and to date, 10 HRC syndromes have been. Exploratory subgroup analysis of 3-arm phase III trial comparing temsirolimus, interferon-α or both including 55 papillary RCCs revealed that temsirolimus group had prolonged overall survival and progression-free survival compared to patients treated with interferon-α [18] Another potential agent might be erlotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. A multicenter phase IItrial of erlotinib in patients with locally advanced and metastatic papillary RCCs revealed an overall response rate of 11% with an additional 53% experiencing stable disease [19]. These data are not specific for HLRCC. When a germline mutation is identified, all family members should be offered appropriate counseling and genetic testing
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