Hereditary Gastric Cancer: Single-Gene or Multigene Panel Testing? A Mono-Institutional Experience
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients’ Selection
2.2. DNA Extraction and Quantification
2.3. Single Gene Testing
2.4. MGPT Using Hereditary Cancer Solution by Sophia Genetics
2.5. Variant Classification
2.6. Statistical Analysis
3. Results
3.1. Description of GC Patients
3.2. SGT Results
3.3. MGPT Results
3.4. Age Distribution and GC Histological Classification in PV Carriers
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AJCC | American Joint Committee on Cancer |
BC | breast cancer |
CRC | colorectal adenocarcinoma |
DGC | diffuse gastric cancer |
FAP | Familial Adenomatous Polyposis |
FH | family history |
FIGC | Familial Intestinal Gastric Cancer |
GAPPS | Gastric Adenocarcinoma and Proximal Polyposis of the Stomach |
GC | gastric cancer |
GIST | gastrointestinal stromal tumor |
H. pylori | Helicobacter pylori |
HBOC | Hereditary Breast and Ovarian Cancer |
HDGC | Hereditary Diffuse Gastric Cancer |
HR | Homologous Recombination |
IARC | International Agency for Research on Cancer |
IEO | European Institute of Oncology |
IGC | intestinal gastric cancer |
IGCLC | International Gastric Cancer Linkage Consortium |
IQR | interquartile range |
LOVD | Leiden Open Variation Database |
LS | Lynch syndrome |
MGPT | multigene panel testing |
MMR | mismatch repair |
MSI | microsatellite instability |
PH | personal history |
PARPi | poly (ADP-ribose) polymerase inhibitors |
PV | pathogenic variant |
SGT | single gene testing |
VUS | variant of unknown significance |
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Variables | N° | % |
---|---|---|
Sex | ||
Male | 17 | 31.5% |
Female | 37 | 68.5% |
Age at diagnosis | ||
<50 | 40 | 74.1% |
≥50 | 14 | 25.9% |
Histology according to Lauren | ||
Diffuse | 33 | 61.1% |
Intestinal | 8 | 14.8% |
Mixed | 8 | 14.8% |
Unknown | 5 | 9.3% |
Anatomic location | ||
Cardia | 7 | 12.9% |
Non-cardia | 42 | 77.8% |
Unknown | 5 | 9.3% |
H. pylori infection | ||
Yes | 11 | 20.4% |
No | 9 | 16.7% |
Unknown | 34 | 62.9% |
AJCC Staging at diagnosis | ||
Early Stage | 27 | 50.0% |
Late Stage | 24 | 44.4% |
Unknown | 3 | 5.6% |
Other tumors | ||
Yes | 14 | 25.9% |
No | 40 | 74.1% |
Family history of GC | ||
Yes | 27 | 50.0% |
No | 26 | 48.1% |
Unknown | 1 | 1.9% |
N° | % | |
---|---|---|
SGT * | ||
Yes | 50 | 92.6% |
Genes analyzed by SGT * | ||
CDH1 | 43 | 86.0% |
BRCA1, BRCA2 | 9 | 18.0% |
MLH1, PMS2 | 10 | 20.0% |
MSH2, MSH6, EPCAM ** | 11 | 22.0% |
SGT * results | ||
positive | 7 | 14.0% |
CDH1 | 3 | |
BRCA2 | 2 | |
BRCA1 | 1 | |
MSH2 | 1 | |
uncertain | 1 | 2.0% |
uninformative | 42 | 84.0% |
MGPT | ||
Yes | 37 | 68.5% |
No | 17 | 31.5% |
MGPT results | ||
positive | 5 | 13.5% |
CDH1 | 1 | |
BRCA2 | 1 | |
MSH2 | 1 | |
ATM | 1 | |
RAD51D | 1 | |
uncertain | 13 | 35.1% |
uninformative | 19 | 51.4% |
ID | Gene | cDNA Variant * | Protein Variant | Classification | Gene Testing Approach |
---|---|---|---|---|---|
2 | MSH2 | c.1216C>T | p.Arg406Ter | pathogenic | SGT |
7 | BRCA2 | c.8633-1G>A | p.? | likely pathogenic | SGT |
13 | RAD51D | c.1A>G | p.Met1Val | likely pathogenic | MGPT |
23 | MSH2 | c.339_340del | p.Asn115Ter | pathogenic | SGT/MGPT |
24 | BRCA1 | c.5278-2A>T | p.? | likely pathogenic | SGT |
38 | CDH1 | c.1792C>T | p.Arg598Ter | pathogenic | SGT |
40 | CDH1 | c.833-476_1138-464del | p.Gly278ValfsTer7 | pathogenic | SGT |
42 | ATM | c.2413C>T | p.Arg805Ter | pathogenic | MGPT |
48 | BRCA2 | c.67+1G>A | p.? | likely pathogenic | SGT |
49 | BRCA2 | c.67+1G>A | p.? | likely pathogenic | SGT/MGPT |
53 | CDH1 | c.2416G>T | p.Glu806Ter | likely pathogenic | SGT/MGPT |
Variables | All (n = 37) | CARRIERS (n = 5) | NON-CARRIERS (n = 32) | p-Value |
---|---|---|---|---|
Sex | ||||
Male | 14 (100) | 3 (21.43) | 11 (78.58) | |
Female | 23 (100) | 2 (8.70) | 21 (91.30) | 0.346 |
Median age and IQR (year) | 42 (34–49) | 51 (48–59) | 42 (34–48) | 0.095 |
Age at diagnosis | ||||
<50 | 28 (100) | 2 (7.14) | 26 (92.86) | |
≥50 | 9 (100) | 3 (33.33) | 6 (66.67) | 0.081 |
Smoking § | ||||
Ever | 15 (100) | 1 (6.67) | 14 (93.33) | |
Never | 20 (100) | 3 (15.00) | 17 (85.00) | 0.619 |
Unknown | 2 (100) | 1 (50.00) | 1 (50.00) | |
Alcohol § | ||||
Yes | 21 (100) | 3 (13.64) | 19 (86.36) | |
No | 13 (100) | 1 (7.69) | 12 (92.31) | 1.000 |
Unknown | 2 (50.00) | 1 (50.00) | 1 (50.00) | |
H. pylori infection | ||||
Yes | 8 (100) | 1 (12.50) | 7 (87.50) | |
No | 7 (100) | 0 (0.00) | 7 (100.00) | 0.802 |
Unknown | 22 (100) | 4 (18.18) | 18 (81.82) | |
Histology according to Lauren | ||||
Diffuse | 24 (100) | 2 (8.33) | 22 (91.67) | |
Intestinal | 3 (100) | 2 (66.67) | 1 (33.33) | 0.075 |
Mixed | 5 (100) | 0 (0.00) | 5 (100.00) | |
Unknown | 4 (100) | 1 (20.00) | 4 (80.00) | |
Anatomic location | ||||
Cardia | 6 (100) | 0 (0.00) | 6 (100.00) | |
Non-Cardia | 31 (100) | 5 (16.13) | 26 (83.87) | 0.567 |
AJCC Staging at diagnosis | ||||
Early Stage | 18 (100) | 3 (16.67) | 15 (83.33) | |
Late Stage | 18 (100) | 2 (11.11) | 16 (88.89) | |
Unknown | 1 (100) | 0 (0.00) | 1 (100.00) | 1.000 |
Other tumors | ||||
Yes | 8 (100) | 3 (37.50) | 5 (62.50) | |
No | 29 (100) | 2 (6.90) | 27 (93.10) | 0.057 |
Family History | ||||
Yes | 31 (100) | 5 (16.19) | 26 (83.87) | |
No | 5 (100) | 0 (0.00) | 5 (100.00) | 1.000 |
Unknown | 1 (100) | 0 (0.00) | 1 (100.00) | |
GC | 18 (100) | 5 (27.78) | 13 (72.22) | |
Non GC | 18 (100) | 0 (0.00) | 18 (100.00) | 0.045 |
HBOC-related * | 17 (100) | 3 (17.65) | 14 (82.35) | |
Non HBOC-related | 19 (100) | 2 (10.53) | 17 (89.47) | 0.650 |
LS-related * | 12 (100) | 4 (33.33) | 8 (66.67) | |
Non LS-related | 24 (100) | 1 (4.17) | 23 (95.3) | 0.036 |
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Calvello, M.; Marabelli, M.; Gandini, S.; Marino, E.; Bernard, L.; Dal Molin, M.; Di Cola, G.; Zanzottera, C.; Corso, G.; Fazio, N.; et al. Hereditary Gastric Cancer: Single-Gene or Multigene Panel Testing? A Mono-Institutional Experience. Genes 2023, 14, 1077. https://doi.org/10.3390/genes14051077
Calvello M, Marabelli M, Gandini S, Marino E, Bernard L, Dal Molin M, Di Cola G, Zanzottera C, Corso G, Fazio N, et al. Hereditary Gastric Cancer: Single-Gene or Multigene Panel Testing? A Mono-Institutional Experience. Genes. 2023; 14(5):1077. https://doi.org/10.3390/genes14051077
Chicago/Turabian StyleCalvello, Mariarosaria, Monica Marabelli, Sara Gandini, Elena Marino, Loris Bernard, Matteo Dal Molin, Giulia Di Cola, Cristina Zanzottera, Giovanni Corso, Nicola Fazio, and et al. 2023. "Hereditary Gastric Cancer: Single-Gene or Multigene Panel Testing? A Mono-Institutional Experience" Genes 14, no. 5: 1077. https://doi.org/10.3390/genes14051077