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Germline TP53 Mutation and Clinical Characteristics of Korean Patients With Li-Fraumeni Syndrome

최현정|김종원|기창석|서순팔|박경진
대한진단검사의학회 (Korean Society For Laboratory Medicine)|2016.09|Annals of Laboratory Medicine|제36권 제5호|pp. 463-468

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키워드

TP53Germline mutationLi-Fraumeni syndrome
주제분류병리학

초록

Background: Little is known of the mutation and tumor spectrum of Korean patients with Li-Fraumeni syndrome (LFS). Owing to the rarity of LFS, few cases have been reported in Korea thus far. This study aimed to retrospectively review the mutations and clinical characteristics of Korean patients with LFS. Methods: TP53 mutation was screened in 89 unrelated individuals at the Samsung Medical Center in Korea, from 2004 to 2015. Six additional mutation carriers were obtained from the literature. Results: We identified nine different mutations in 14 Korean patients (male to female ratio=0.3:1). Two such frameshift mutations (p.Pro98Leufs*25, p.Pro27Leufs*17) were novel. The recurrent mutations were located at codons 31 (n=2; p.Val31Ile), 175 (n=3; p.Arg175His), and 273 (n=4; p.Arg273His and p.Arg273Cys). The median age at the first tumor onset was 25 yr. Ten patients (71%) developed multiple primary tumors. A diverse spectrum of tumors was observed, including breast (n=6), osteosarcoma (n=4), brain (n=4), leukemia (n=2), stomach (n=2), thyroid (n=2), lung (n=2), skin (n=2), bladder (n=1), nasal cavity cancer (n=1), and adrenocortical carcinoma (n=1). Conclusions: There was considerable heterogeneity in the TP53 mutations and tumor spectrum in Korean patients with LFS. Our results suggest shared and different LFS characteristics between Caucasian and Korean patients. This is the first report on the mutation spectrum and clinical characteristics from the largest series of Korean LFS patients.

Abstract

Background: Little is known of the mutation and tumor spectrum of Korean patients with Li-Fraumeni syndrome (LFS). Owing to the rarity of LFS, few cases have been reported in Korea thus far. This study aimed to retrospectively review the mutations and clinical characteristics of Korean patients with LFS. Methods: TP53 mutation was screened in 89 unrelated individuals at the Samsung Medical Center in Korea, from 2004 to 2015. Six additional mutation carriers were obtained from the literature. Results: We identified nine different mutations in 14 Korean patients (male to female ratio=0.3:1). Two such frameshift mutations (p.Pro98Leufs*25, p.Pro27Leufs*17) were novel. The recurrent mutations were located at codons 31 (n=2; p.Val31Ile), 175 (n=3; p.Arg175His), and 273 (n=4; p.Arg273His and p.Arg273Cys). The median age at the first tumor onset was 25 yr. Ten patients (71%) developed multiple primary tumors. A diverse spectrum of tumors was observed, including breast (n=6), osteosarcoma (n=4), brain (n=4), leukemia (n=2), stomach (n=2), thyroid (n=2), lung (n=2), skin (n=2), bladder (n=1), nasal cavity cancer (n=1), and adrenocortical carcinoma (n=1). Conclusions: There was considerable heterogeneity in the TP53 mutations and tumor spectrum in Korean patients with LFS. Our results suggest shared and different LFS characteristics between Caucasian and Korean patients. This is the first report on the mutation spectrum and clinical characteristics from the largest series of Korean LFS patients.

참고문헌 (25)

  1. Li FP, "A cancer family syndrome in twenty-four kindreds", Cancer Res, 48, pp.5358~5362 (1988)
  2. Malkin D, "Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms", Science, 250, pp.1233~1238 (1990)
  3. Ruijs MW, "TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes", J Med Genet, 47, pp.421~428 (2010)
  4. Masciari S, "Gastric cancer in individuals with Li-Fraumeni syndrome", Genet Med, 13, pp.651~657 (2011)
  5. Michalarea V, "EGFR-mutated lung cancer in Li-Fraumeni syndrome", Lung Cancer, 85, pp.485~487 (2014)
  6. Ricordel C, "EFGR-mutant lung adenocarcinoma and Li-Fraumeni syndrome: report of two cases and review of the literature", Lung Cancer, 87, pp.80~84 (2015)
  7. Petitjean A, "Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database", Hum Mutat, 28, pp.622~629 (2007)
  8. Bougeard G, "Revisiting Li-Fraumeni syndrome from TP53 mutation carriers", J Clin Oncol, 33, pp.2345~2352 (2015)
  9. Malkin D, "Li-fraumeni syndrome", Genes Cancer, 2, pp.475~484 (2011)
  10. Nichols KE, "Genotype versus phenotype: The yin and yang of germline TP53 mutations in Li-Fraumeni syndrome", J Clin Oncol, 33, pp.2331~2333 (2015)
  11. Bang YJ, "The first documentation of Li-Fraumeni syndrome in Korea", J Korean Med Sci, 10, pp.205~210 (1995)
  12. Kim IJ, "A TP53-truncating germline mutation (E287X) in a family with characteristics of both hereditary diffuse gastric cancer and Li-Fraumeni syndrome", J Hum Genet, 49, pp.591~595 (2004)
  13. 황상미, "가족성 암 증후군이 의심되는 환자에서 유전 상담의 영향: TP53 유전자 돌연변이가 확인된 Li-Fraumeni 유사 증후군 환자를 통한 증례 보고", Annals of Laboratory Medicine, 28(6), pp.493~497 (2008), 대한진단검사의학회
  14. Shin HJ, "Family of Li-Fraumeni syndrome with a germline mutation in the p53 gene", Clin Pediatr Hematol Oncol, 16, pp.38~42 (2009)
  15. 조용근, "A Case of Late-Onset Li-Fraumeni–like Syndrome with Unilateral Breast Cancer", Annals of Laboratory Medicine, 33(3), pp.212~216 (2013), 대한진단검사의학회
  16. Oh CS, "Osteosarcoma with adenocarcinoma of lung in Li-Fraumeni syndrome: a case report", J Korean Bone Joint Tumor Soc, 20, pp.99~103 (2014)
  17. Cho Y, "Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations", Science, 265, pp.346~355 (1994)
  18. Achatz MI, "The TP53 mutation, R337H, is associated with Li-Fraumeni and Li-Fraumeni-like syndromes in Brazilian families", Cancer Lett, 245, pp.96~102 (2007)
  19. Gonzalez KD, "Beyond Li Fraumeni Syndrome: clinical characteristics of families with p53 germline mutations", J Clin Oncol, 27, pp.1250~1256 (2009)
  20. Sagne C, "Age at cancer onset in germline TP53 mutation carriers: association with polymorphisms in predicted G-quadruplex structures", Carcinogenesis, 35, pp.807~815 (2014)
  21. Bond GL, "A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans", Cell, 119, pp.591~602 (2004)
  22. Ariffin H, "Frequent occurrence of gastric cancer in Asian kindreds with Li-Fraumeni syndrome", Clin Genet, 88, pp.450~455 (2015)
  23. Mouchawar J, "Population-based estimate of the contribution of TP53 mutations to subgroups of early-onset breast cancer: Australian Breast Cancer Family Study", Cancer Res, 70, pp.4795~4800 (2010)
  24. McCuaig JM, "Routine TP53 testing for breast cancer under age 30: ready for prime time?", Fam Cancer, 11, pp.607~613 (2012)
  25. Melhem-Bertrandt A, "Early onset HER2-positive breast cancer is associated with germline TP53 mutations", Cancer, 118, pp.908~913 (2012)

관련 논문AI추천

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