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2. Role of germline aberrations affecting CTNNA1, MAP3K6 and MYD88 in gastric cancer susceptibility

Author

Weren, RDA, van der Post, RS, Vogelaar, IP, Van Krieken, JH, Spruijt, L, Lubinski, J, Jakubowska, A, Teodorczyk, U, Aalfs, CM, Hest, LP, Oliveira, C, Kamping, EJ, Schackert, HK, Ranzani, GN, Garcia, EBG, Hes, FJ, Holinski-Feder, E, Genuardi, M, Ausems, M, Sijmons, RH, Wagner, Anja, van der Kolk, LE, Cats, A, Bjornevoll, I, Hoogerbrugge, N, Ligtenberg, MJL, Weren, RDA, van der Post, RS, Vogelaar, IP, Van Krieken, JH, Spruijt, L, Lubinski, J, Jakubowska, A, Teodorczyk, U, Aalfs, CM, Hest, LP, Oliveira, C, Kamping, EJ, Schackert, HK, Ranzani, GN, Garcia, EBG, Hes, FJ, Holinski-Feder, E, Genuardi, M, Ausems, M, Sijmons, RH, Wagner, Anja, van der Kolk, LE, Cats, A, Bjornevoll, I, Hoogerbrugge, N, and Ligtenberg, MJL

Published
2018

3. Role of germline aberrations affecting CTNNA1, MAP3K6 and MYD88 in gastric cancer susceptibility.

Author

Weren, Rda, van der Post, R, Vogelaar, Ip, van Krieken, Jh, Spruijt, L, Lubinski, J, Jakubowska, A, Teodorczyk, U, Aalfs, Cm, van Hest, Lp, Oliveira, C, Kamping, Ej, Schackert, Hk, Ranzani, Gn, Gómez García, Eb, Hes, Fj, Holinski-Feder, E, Genuardi, Maurizio, Ausems, Mgem, Sijmons, Rh, Wagner, A, van der Kolk, Le, Cats, A, Bjørnevoll, I, Hoogerbrugge, N, Ligtenberg, Mjl., Genuardi M (ORCID:0000-0002-7410-8351), Weren, Rda, van der Post, R, Vogelaar, Ip, van Krieken, Jh, Spruijt, L, Lubinski, J, Jakubowska, A, Teodorczyk, U, Aalfs, Cm, van Hest, Lp, Oliveira, C, Kamping, Ej, Schackert, Hk, Ranzani, Gn, Gómez García, Eb, Hes, Fj, Holinski-Feder, E, Genuardi, Maurizio, Ausems, Mgem, Sijmons, Rh, Wagner, A, van der Kolk, Le, Cats, A, Bjørnevoll, I, Hoogerbrugge, N, Ligtenberg, Mjl., and Genuardi M (ORCID:0000-0002-7410-8351)

Abstract

BACKGROUND: In approximately 10% of all gastric cancer (GC) cases, a heritable cause is suspected. A subset of these cases have a causative germline CDH1 mutation; however, in most cases the cause remains unknown. Our objective was to assess to what extent these remaining cases may be explained by germline mutations in the novel candidate GC predisposing genes CTNNA1, MAP3K6 or MYD88. METHODS: We sequenced a large cohort of unexplained young and/or familial patients with GC (n=286) without a CDH1germline mutation for germline variants affecting CTNNA1, MAP3K6 and MYD88 using a targeted next-generation sequencing approach based on single-molecule molecular inversion probes. RESULTS: Predicted deleterious germline variants were not encountered in MYD88, but recurrently observed in CTNNA1 (n=2) and MAP3K6 (n=3) in our cohort of patients with GC. In contrast to deleterious variants in CTNNA1, deleterious variants in MAP3K6 also occur frequently in the general population. CONCLUSIONS: Based on our results MAP3K6 should no longer be considered a GC predisposition gene, whereas deleterious CTNNA1 variants are confirmed as an infrequent cause of GC susceptibility. Biallelic MYD88 germline mutations are at most a very rare cause of GC susceptibility as no additional cases were identified. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Published
2018

4. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers

Author

van der Post, RS, Vogelaar, IP, Carneiro, F, Guilford, P, Huntsman, D, Hoogerbrugge, N, Caldas, C, Schreiber, KEC, Hardwick, RH, Ausems, MGEM, Bardram, L, Benusiglio, PR, Bisseling, TM, Blair, V, Bleiker, E, Boussioutas, A, Cats, A, Coit, D, DeGregorio, L, Figueiredo, J, Ford, JM, Heijkoop, E, Hermens, R, Humar, B, Kaurah, P, Keller, G, Lai, J, Ligtenberg, MJL, O'Donovan, M, Oliveira, C, Pinheiro, H, Ragunath, K, Rasenberg, E, Richardson, S, Roviello, F, Schackert, H, Seruca, R, Taylor, A, ter Huurne, A, Tischkowitz, M, Joe, STA, van Dijck, B, van Grieken, NCT, van Hillegersberg, R, van Sandick, JW, Vehof, R, van Krieken, JH, Fitzgerald, RC, van der Post, RS, Vogelaar, IP, Carneiro, F, Guilford, P, Huntsman, D, Hoogerbrugge, N, Caldas, C, Schreiber, KEC, Hardwick, RH, Ausems, MGEM, Bardram, L, Benusiglio, PR, Bisseling, TM, Blair, V, Bleiker, E, Boussioutas, A, Cats, A, Coit, D, DeGregorio, L, Figueiredo, J, Ford, JM, Heijkoop, E, Hermens, R, Humar, B, Kaurah, P, Keller, G, Lai, J, Ligtenberg, MJL, O'Donovan, M, Oliveira, C, Pinheiro, H, Ragunath, K, Rasenberg, E, Richardson, S, Roviello, F, Schackert, H, Seruca, R, Taylor, A, ter Huurne, A, Tischkowitz, M, Joe, STA, van Dijck, B, van Grieken, NCT, van Hillegersberg, R, van Sandick, JW, Vehof, R, van Krieken, JH, and Fitzgerald, RC

Abstract

Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patient's perspective on multiple aspects, including diet post gastrectomy. The updated guidelines include revised CDH1 testing criteria (taking into account first-degree and second-degree relatives): (1) families with two or more patients with gastric cancer at any age, one confirmed DGC; (2) individuals with DGC before the age of 40 and (3) families with diagnoses of both DGC and LBC (one diagnosis before the age of 50). Additionally, CDH1 testing could be considered in patients with bilateral or familial LBC before the age of 50, patients with DGC and cleft lip/palate, and those with precursor lesions for signet ring cell carcinoma. Given the high mortality associated with invasive disease, prophylactic total gastrectomy at a centre of expertise is advised for individuals with pathogenic CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation is recommended. Standardised endoscopic surveillance in experienced centres is recommended for those opting not to have gastrectomy at the current time, those with CDH1 variants of uncertain significance and those that fulfil hereditary DGC criteria without germline CDH1 mutations. Expert histopathological confirmation of (early) signet ring cell carcinoma is recommended. The impact of gastrectomy and mastectomy should not be underestimated; these can have severe consequences on a psychological, physiological and metabolic level. Nutritional problems should be carefully monitored.

Published
2015

5. EURECCA colorectal: multidisciplinary management: European consensus conference colon & rectum

Author

Van De Velde, Cjh, Boelens, Pg, Borras, Jm, Coebergh, J, Cervantes, A, Blomqvist, L, Beets Tan, Rgh, Van Den Broek, Cbm, Brown, G, Van Cutsem, E, Espin, E, Haustermans, K, Glimelius, B, Iversen, Lh, Van Krieken, Jh, Marijnen, Cam, Henning, G, Gore Booth, J, Meldolesi, Elisa, Mroczkowski, P, Nagtegaal, I, Naredi, P, Ortiz, H, Påhlman, L, Quirke, P, Rödel, C, Roth, A, Rutten, H, Schmoll, Hj, Smith, Jj, Tanis, Pj, Taylor, C, Wibe, A, Wiggers, T, Gambacorta, Maria Antonietta, Aristei, C, Valentini, Vincenzo, Gambacorta, Maria Antonietta (ORCID:0000-0001-5455-8737), Valentini, Vincenzo (ORCID:0000-0003-4637-6487), Van De Velde, Cjh, Boelens, Pg, Borras, Jm, Coebergh, J, Cervantes, A, Blomqvist, L, Beets Tan, Rgh, Van Den Broek, Cbm, Brown, G, Van Cutsem, E, Espin, E, Haustermans, K, Glimelius, B, Iversen, Lh, Van Krieken, Jh, Marijnen, Cam, Henning, G, Gore Booth, J, Meldolesi, Elisa, Mroczkowski, P, Nagtegaal, I, Naredi, P, Ortiz, H, Påhlman, L, Quirke, P, Rödel, C, Roth, A, Rutten, H, Schmoll, Hj, Smith, Jj, Tanis, Pj, Taylor, C, Wibe, A, Wiggers, T, Gambacorta, Maria Antonietta, Aristei, C, Valentini, Vincenzo, Gambacorta, Maria Antonietta (ORCID:0000-0001-5455-8737), and Valentini, Vincenzo (ORCID:0000-0003-4637-6487)

Abstract

Care for patients with colon and rectal cancer has improved in the last 20years; however considerable variation still exists in cancer management and outcome between European countries. Large variation is also apparent between national guidelines and patterns of cancer care in Europe. Therefore, EURECCA, which is the acronym of European Registration of Cancer Care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012, the first multidisciplinary consensus conference about cancer of the colon and rectum was held. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries.

Published
2014

6. EURECCA colorectal: multidisciplinary management: European consensus conference colon & rectum

Author

Van De Velde, Cjh, Boelens, Pg, Borras, Jm, Coebergh, J, Cervantes, A, Blomqvist, L, Beets Tan, Rgh, Van Den Broek, Cbm, Brown, G, Van Cutsem, E, Espin, E, Haustermans, K, Glimelius, B, Iversen, Lh, Van Krieken, Jh, Marijnen, Cam, Henning, G, Gore Booth, J, Meldolesi, Elisa, Mroczkowski, P, Nagtegaal, I, Naredi, P, Ortiz, H, Påhlman, L, Quirke, P, Rödel, C, Roth, A, Rutten, H, Schmoll, Hj, Smith, Jj, Tanis, Pj, Taylor, C, Wibe, A, Wiggers, T, Gambacorta, Maria Antonietta, Aristei, C, Valentini, Vincenzo, Gambacorta, Maria Antonietta (ORCID:0000-0001-5455-8737), Valentini, Vincenzo (ORCID:0000-0003-4637-6487), Van De Velde, Cjh, Boelens, Pg, Borras, Jm, Coebergh, J, Cervantes, A, Blomqvist, L, Beets Tan, Rgh, Van Den Broek, Cbm, Brown, G, Van Cutsem, E, Espin, E, Haustermans, K, Glimelius, B, Iversen, Lh, Van Krieken, Jh, Marijnen, Cam, Henning, G, Gore Booth, J, Meldolesi, Elisa, Mroczkowski, P, Nagtegaal, I, Naredi, P, Ortiz, H, Påhlman, L, Quirke, P, Rödel, C, Roth, A, Rutten, H, Schmoll, Hj, Smith, Jj, Tanis, Pj, Taylor, C, Wibe, A, Wiggers, T, Gambacorta, Maria Antonietta, Aristei, C, Valentini, Vincenzo, Gambacorta, Maria Antonietta (ORCID:0000-0001-5455-8737), and Valentini, Vincenzo (ORCID:0000-0003-4637-6487)

Abstract

Care for patients with colon and rectal cancer has improved in the last 20years; however considerable variation still exists in cancer management and outcome between European countries. Large variation is also apparent between national guidelines and patterns of cancer care in Europe. Therefore, EURECCA, which is the acronym of European Registration of Cancer Care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012, the first multidisciplinary consensus conference about cancer of the colon and rectum was held. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries.

Published
2014

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