Germline CDH1 mutations in bilateral lobular carcinoma in situ

C Petridis; I Shinomiya; K. Kohut; P Gorman; M Caneppele; V Shah; M Troy; S E Pinder; A Hanby; I Tomlinson; R C Trembath; R Roylance; M A Simpson; E J Sawyer

doi:10.1038/bjc.2013.792

Germline CDH1 mutations in bilateral lobular carcinoma in situ

C Petridis, I Shinomiya, K. Kohut, P Gorman, M Caneppele, V Shah, M Troy, S E Pinder, A Hanby, I Tomlinson, R C Trembath, R Roylance, M A Simpson, E J Sawyer

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Invasive lobular breast cancer (ILC) and lobular carcinoma in situ (LCIS) are characterised by loss of E-cadherin expression. However germline CDH1 mutations are rare in cases of ILC with no family history of hereditary diffuse gastric cancer (HDGC) and have not been described in women with LCIS.

Methods: We screened the CDH1 gene in 50 cases of bilateral LCIS/ILC using Sanger sequencing and MLPA.

Results: Sanger sequencing revealed four pathogenic germline mutations, including a novel splicing mutation (c.48+1G>A). The remaining three (c.1465insC, c.1942G>T, c.2398delC) have been previously described. All four cases had bilateral LCIS +/− ILC and no family history of gastric cancer.

Conclusion: CDH1 germline mutations have not been previously described in women with LCIS. We have shown that germline CDH1 mutations are associated with early onset of bilateral LCIS with or without ILC in women without a family history of gastric cancer. CDH1 mutation screening should be considered in women with early onset of bilateral LCIS/ILC with no family history of HDGC.

Original language	English
Pages (from-to)	1053-1057
Number of pages	5
Journal	BJC: British Journal of Cancer
Volume	110
Issue number	4
Early online date	24 Dec 2013
DOIs	https://doi.org/10.1038/bjc.2013.792
Publication status	Published - 18 Feb 2014

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10.1038/bjc.2013.792

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title = "Germline CDH1 mutations in bilateral lobular carcinoma in situ",

abstract = "Background: Invasive lobular breast cancer (ILC) and lobular carcinoma in situ (LCIS) are characterised by loss of E-cadherin expression. However germline CDH1 mutations are rare in cases of ILC with no family history of hereditary diffuse gastric cancer (HDGC) and have not been described in women with LCIS.Methods: We screened the CDH1 gene in 50 cases of bilateral LCIS/ILC using Sanger sequencing and MLPA.Results: Sanger sequencing revealed four pathogenic germline mutations, including a novel splicing mutation (c.48+1G>A). The remaining three (c.1465insC, c.1942G>T, c.2398delC) have been previously described. All four cases had bilateral LCIS +/− ILC and no family history of gastric cancer.Conclusion: CDH1 germline mutations have not been previously described in women with LCIS. We have shown that germline CDH1 mutations are associated with early onset of bilateral LCIS with or without ILC in women without a family history of gastric cancer. CDH1 mutation screening should be considered in women with early onset of bilateral LCIS/ILC with no family history of HDGC.",

author = "C Petridis and I Shinomiya and K. Kohut and P Gorman and M Caneppele and V Shah and M Troy and Pinder, {S E} and A Hanby and I Tomlinson and Trembath, {R C} and R Roylance and Simpson, {M A} and Sawyer, {E J}",

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doi = "10.1038/bjc.2013.792",

language = "English",

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TY - JOUR

T1 - Germline CDH1 mutations in bilateral lobular carcinoma in situ

AU - Petridis, C

AU - Shinomiya, I

AU - Kohut, K.

AU - Gorman, P

AU - Caneppele, M

AU - Shah, V

AU - Troy, M

AU - Pinder, S E

AU - Hanby, A

AU - Tomlinson, I

AU - Trembath, R C

AU - Roylance, R

AU - Simpson, M A

AU - Sawyer, E J

PY - 2014/2/18

Y1 - 2014/2/18

N2 - Background: Invasive lobular breast cancer (ILC) and lobular carcinoma in situ (LCIS) are characterised by loss of E-cadherin expression. However germline CDH1 mutations are rare in cases of ILC with no family history of hereditary diffuse gastric cancer (HDGC) and have not been described in women with LCIS.Methods: We screened the CDH1 gene in 50 cases of bilateral LCIS/ILC using Sanger sequencing and MLPA.Results: Sanger sequencing revealed four pathogenic germline mutations, including a novel splicing mutation (c.48+1G>A). The remaining three (c.1465insC, c.1942G>T, c.2398delC) have been previously described. All four cases had bilateral LCIS +/− ILC and no family history of gastric cancer.Conclusion: CDH1 germline mutations have not been previously described in women with LCIS. We have shown that germline CDH1 mutations are associated with early onset of bilateral LCIS with or without ILC in women without a family history of gastric cancer. CDH1 mutation screening should be considered in women with early onset of bilateral LCIS/ILC with no family history of HDGC.

AB - Background: Invasive lobular breast cancer (ILC) and lobular carcinoma in situ (LCIS) are characterised by loss of E-cadherin expression. However germline CDH1 mutations are rare in cases of ILC with no family history of hereditary diffuse gastric cancer (HDGC) and have not been described in women with LCIS.Methods: We screened the CDH1 gene in 50 cases of bilateral LCIS/ILC using Sanger sequencing and MLPA.Results: Sanger sequencing revealed four pathogenic germline mutations, including a novel splicing mutation (c.48+1G>A). The remaining three (c.1465insC, c.1942G>T, c.2398delC) have been previously described. All four cases had bilateral LCIS +/− ILC and no family history of gastric cancer.Conclusion: CDH1 germline mutations have not been previously described in women with LCIS. We have shown that germline CDH1 mutations are associated with early onset of bilateral LCIS with or without ILC in women without a family history of gastric cancer. CDH1 mutation screening should be considered in women with early onset of bilateral LCIS/ILC with no family history of HDGC.

U2 - 10.1038/bjc.2013.792

DO - 10.1038/bjc.2013.792

M3 - Article

SN - 0007-0920

VL - 110

SP - 1053

EP - 1057

JO - BJC: British Journal of Cancer

JF - BJC: British Journal of Cancer

IS - 4

ER -

Germline CDH1 mutations in bilateral lobular carcinoma in situ

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