Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity): Joint recommendations of Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC), and Variant Interpretation for Cancer Consortium (VICC)

被引：146

作者：

Horak, Peter ^{[1
]}

Griffith, Malachi ^{[2
]}

Danos, Arpad M. ^{[2
]}

Pitel, Beth A. ^{[3
]}

Madhavan, Subha ^{[4
]}

Liu, Xuelu ^{[5
]}

Chow, Cynthia ^{[6
]}

Williams, Heather ^{[7
]}

Carmody, Leigh ^{[8
]}

Barrow-Laing, Lisa ^{[9
]}

Rieke, Damian ^{[10
]}

Kreutzfeldt, Simon ^{[1
]}

Stenzinger, Albrecht ^{[11
]}

Tamborero, David ^{[12
]}

Benary, Manuela ^{[10
]}

Rajagopal, Padma Sheila ^{[13
]}

Ida, Cristiane M. ^{[3
]}

Lesmana, Harry ^{[14
]}

Satgunaseelan, Laveniya ^{[15
]}

Merker, Jason D. ^{[16
]}

Tolstorukov, Michael Y. ^{[5
]}

Campregher, Paulo Vidal ^{[17
]}

Warner, Jeremy L. ^{[18
]}

Rao, Shruti ^{[4
]}

Natesan, Maya ^{[2
]}

Shen, Haolin ^{[2
]}

Venstrom, Jeffrey ^{[19
]}

Roy, Somak ^{[20
]}

Tao, Kayoko ^{[21
]}

Kanagal-Shamanna, Rashmi ^{[22
]}

Xu, Xinjie ^{[3
]}

Ritter, Deborah, I ^{[23
]}

Pagel, Kym ^{[24
]}

Krysiak, Kilannin ^{[2
]}

Dubuc, Adrian ^{[25
]}

Akkari, Yassmine M. ^{[26
]}

Li, Xuan Shirley ^{[27
]}

Lee, Jennifer ^{[28
]}

King, Ian ^{[29
]}

Raca, Gordana ^{[30
]}

Wagner, Alex H. ^{[31
,32
]}

Li, Marylin M. ^{[33
]}

Plon, Sharon E. ^{[23
]}

Kulkarni, Shashikant ^{[23
]}

Griffith, Obi L. ^{[2
]}

Chakravarty, Debyani ^{[34
]}

Sonkin, Dmitriy ^{[35
,36
]}

机构：

[1] German Canc Res Ctr, Natl Ctr Tumor Dis NCT, Heidelberg, Germany

[2] Washington Univ, Sch Med, St Louis, MO USA

[3] Mayo Clin, Rochester, MN USA

[4] Georgetown Univ Med Ctr, Washington, DC USA

[5] Dana Farber Canc Inst, Boston, MA 02115 USA

[6] BC Canc Agcy, Vancouver, BC, Canada

[7] Columbia Univ, New York, NY USA

[8] Jackson Lab Genom Med, Farmington, CT USA

[9] QIAGEN Inc, Redwood City, CA USA

[10] Charite Univ Med Berlin, Berlin, Germany

[11] Heidelberg Univ, Inst Pathol, Heidelberg, Germany

[12] Karolinska Inst, Stockholm, Sweden

[13] NCI, Canc Data Sci Lab, Ctr Canc Res, Bethesda, MD 20892 USA

[14] Cleveland Clin, Genom Med Inst, Lerner Res Inst, Cleveland, OH 44106 USA

[15] Royal Prince Alfred Hosp, Sydney, NSW, Australia

[16] Univ N Carolina, UNC Sch Med, Chapel Hill, NC 27515 USA

[17] Hosp Israelita Albert Einstein, Sao Paulo, SP, Brazil

[18] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA

[19] Fdn Med Inc, Cambridge, MA USA

[20] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA

[21] Natl Canc Ctr, Tokyo, Japan

[22] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[23] Baylor Coll Med, Houston, TX 77030 USA

[24] Johns Hopkins Univ, Baltimore, MD USA

[25] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA

[26] Legacy Hlth, Portland, OR USA

[27] Congenica Ltd, Cambridge, England

[28] NCI, Frederick Natl Lab Canc Res, Rockville, MD USA

[29] Univ Hlth Network, Toronto, ON, Canada

[30] Univ Southern Calif, Los Angeles, CA 90007 USA

[31] Nationwide Childrens Hosp, Columbus, OH USA

[32] Ohio State Univ, Coll Med, Columbus, OH 43210 USA

[33] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[34] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[35] NCI, Rockville, MD 20850 USA

[36] NCI, Div Canc Treatment & Diag, 9609 Med Ctr Dr, Rockville, MD 20850 USA

来源：

GENETICS IN MEDICINE | 2022年 / 24卷 / 05期

关键词：

22; December; 2021; Cancer genetic testing; Oncogenicity; Pathogenicity; Somatic variant; Variant classi fi cation; TERT PROMOTER MUTATIONS; CONSENSUS-RECOMMENDATION; SEQUENCE VARIANTS; TUMORS; CHEMOTHERAPY; ASSOCIATION; INHIBITION; GUIDELINES; COLLEGE; TOOL;

D O I：

10.1016/j.gim.2022.01.001

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Purpose: Several professional societies have published guidelines for the clinical interpretation of somatic variants, which specifically address diagnostic, prognostic, and therapeutic implications. Although these guidelines for the clinical interpretation of variants include data types that may be used to determine the oncogenicity of a variant (eg, population frequency, functional, and in silico data or somatic frequency), they do not provide a direct, systematic, and comprehensive set of standards and rules to classify the oncogenicity of a somatic variant. This insufficient guidance leads to inconsistent classification of rare somatic variants in cancer, generates variability in their clinical interpretation, and, importantly, affects patient care. Therefore, it is essential to address this unmet need. Methods: Clinical Genome Resource (ClinGen) Somatic Cancer Clinical Domain Working Group and ClinGen Germline/Somatic Variant Subcommittee, the Cancer Genomics Consortium, and the Variant Interpretation for Cancer Consortium used a consensus approach to develop a standard operating procedure (SOP) for the classification of oncogenicity of somatic variants. Results: This comprehensive SOP has been developed to improve consistency in somatic variant classification and has been validated on 94 somatic variants in 10 common cancer-related genes. Conclusion: The comprehensive SOP is now available for classification of oncogenicity of somatic variants. ?? 2022 Published by Elsevier Inc. on behalf of American College of Medical Genetics and

引用

页码：986 / 998

页数：13

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