臨床検査66巻6号

2022年06月発行

今月の特集2 良性腫瘍の病理と遺伝子異常

消化管ポリポーシス

著者： 田村和朗¹²

所属機関： ¹近畿大学大学院総合理工学研究科 ²医療法人渡辺医学会桜橋渡辺病院遺伝子診療センター

ページ範囲：P.747 - P.755

Point

●消化管ポリポーシスには遺伝性・非遺伝性の分類と，腺腫性・過誤腫性・鋸歯状・混合性の病理組織学的分類がある．

●原因遺伝子をもとに癌素因を調べることが可能となったことから，正確な診断のもとに適切な治療法選択が可能となった．

●血縁者は病的バリアントを共有している可能性がある．遺伝形式が異なる場合であってもリスク評価を適切に行うことで，サーベイランスにつなぐことが可能となった．

参考文献

1）Utsunomiya J：The concept of hereditary colorectal cancer and implication of its study. eds. Hereditary colorectal cancer (Utsunomiya J, Lynch HT, eds), Springer-Verlag，pp3-16，1990

2）Tamura K, Utsunomiya J, Iwama T, et al：Mechanism of carcinogenesis in familial tumors. Int J Clin Oncol　9：232-245，2004

3）Valle L：Recent Discoveries in the Genetics of Familial Colorectal Cancer and Polyposis. Clin Gastroenterol Hepatol　15：809-819，2017

4）Valle L, Vilar E, Tavtigian SV, et al：Genetic predisposition to colorectal cancer: syndromes, genes, classification of genetic variants and implications for precision medicine. J Pathol　247：574-588，2019

5）Valle L, de Voer RM, Goldberg Y, et al：Update on genetic predisposition to colorectal cancer and polyposis. Mol Aspects Med　69：10-26，2019

6）Monahan KJ, Bradshaw N, Dolwani S, et al：Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG). Gut　69：411-444，2020

7）Terradas M, Capellá G, Valle L：Dominantly Inherited Hereditary Nonpolyposis Colorectal Cancer Not Caused by MMR Genes. J Clin Med　9：1954，2020

8）大腸癌研究会（編）：遺伝性大腸癌診療ガイドライン　2020年版，金原出版，2020

9）Kim JC, Bodmer WF：Genotypic and Phenotypic Characteristics of Hereditary Colorectal Cancer. Ann Coloproctol　37：368-381，2021

10）Palles C, Cazier JB, Howarth KM, et al：Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet　45：136-144，2013

11）Al-Tassan N, Chmiel NH, Maynard J, et al：Inherited variants of MYH associated with somatic G:C→T:A mutations in colorectal tumors. Nat Genet　30：227-232，2002

12）田村和朗，宇都宮譲二，岩間毅夫，他：hMYH-家族性腺腫性ポリポーシスの新しい責任遺伝子．細胞　35：426-430，2003

13）Banda DM, Nuñez NN, Burnside MA, et al：Repair of 8-oxoG: A mismatches by the MUTYH glycosylase: Mechanism, metals and medicine. Free Radic Biol Med　107：202-215，2017

14）Weren RD, Ligtenberg MJ, Kets CM, et al：A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer. Nat Genet　47：668-671，2015

15）Adam R, Spier I, Zhao B, et al：Exome Sequencing Identifies Biallelic MSH3 Germline Mutations as a Recessive Subtype of Colorectal Adenomatous Polyposis. Am J Hum Genet　99：337-351，2016

16）Wimmer K, Kratz CP, Vasen HF, et al：Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium ‘care for CMMRD’ (C4CMMRD). J Med Genet　51：355-365，2014

17）Tamura K, Kaneda M, Futagawa M, et al：Genetic and genomic basis of the mismatch repair system involved in Lynch syndrome. Int J Clin Oncol　24：999-1011，2019

18）Hearle N, Schumacher V, Menko FH, et al：Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. Clin Cancer Res　12：3209-3215，2006

19）Aretz S, Stienen D, Uhlhaas S, et al：High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome. J Med Genet　44：702-709，2007

20）Tan MH, Mester JL, Ngeow J, et al：Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res　18：400-407，2012

21）Gala MK, Mizukami Y, Le LP, et al：Germline mutations in oncogene-induced senescence pathways are associated with multiple sessile serrated adenomas. Gastroenterology　146：520-529，2014

22）Bond CE, McKeone DM, Kalimutho M：RNF43 and ZNRF3 are commonly altered in serrated pathway colorectal tumorigenesis. Oncotarget　7：70589-70600，2016

23）Whitelaw SC, Murday VA, Tomlinson IP, et al：Clinical and molecular features of the hereditary mixed polyposis syndrome. Gastroenterology　112：327-334，1997

24）Jaeger E, Leedham S, Lewis A, et al：Hereditary mixed polyposis syndrome is caused by a 40-kb upstream duplication that leads to increased and ectopic expression of the BMP antagonist GREM1. Nat Genet　44：699-703，2012